longer after Ven‐Obi therapy compared to Clb‐Obi therapy (median

1225 days versus 227 days, p <2e‐16)(Fig D).

Based on a covariate screening of 28 biological and clinical features,

the ﬁnal model showed a signiﬁcant impact on MRD growth dynamics

by Ven‐Obi treatment, high MRD levels at the start of treatment,

high CLL‐IPI, del11q, higher disease burden, response to treatment,

and IGHV status (Fig E,F).

Conclusion: This analysis establishes a robust, population‐based

model of MRD growth dynamics that allows description of growth

trajectories and treatment effects after treatment cessation. In

addition to more effective MRD eradication with Ven‐Obi, our

results demonstrate that MRD growth is modulated more efﬁciently

by BCL2‐targeting treatment in contrast to genotoxic

chemoimmunotherapy.

The research was funded by: Hoffmann‐La Roche Ltd.; AbbVie Inc.

Keywords: Diagnostic and Prognostic Biomarkers, Chronic Lympho-

cytic Leukemia (CLL)

Conﬂicts of interests pertinent to the abstract

O. Al‐Sawaf

Consultant or advisory role: Roche, Abbvie

Honoraria: Roche, Abbvie

Research funding: Roche, Abbvie

Educational grants: Roche, Abbvie

T. Lu

Employment or leadership position: Genentec Inc.

M. Z. Liao

Employment or leadership position: Genentec Inc.

A. Panchal

Employment or leadership position: Roche Products Ltd.

T. Ching

Employment or leadership position: Adaptive Biotechnologies Corp.

A.‐M. Fink

Honoraria: Celgene, Janssen, Hoffmann‐LaRoche

E. Tausch

Honoraria: Roche AG, AbbVie

M. Ritgen

Honoraria: Hoffmann‐LaRoche, AbbVie

Research funding: Hoffmann‐LaRoche

K.‐A. Kreuzer

Honoraria: Roche, AbbVie

Research funding: Roche, AbbVie

S. Kim

Employment or leadership position: AbbVie Inc.

D. Miles

Employment or leadership position: Genentec Inc.

C. Wendtner

Honoraria: Hoffmann‐LaRoche, AbbVie, Janssen‐Cilag, Gilead,

MorphoSys

S. Stilgenbauer

Honoraria: AbbVie, AstraZeneca, Celgene, Gilead, GSK, Hoffmann‐

LaRoche, Janssen, Novartis, Pharmacyclics, Sunesis, Verastem

Research funding: AbbVie, AstraZeneca, Celgene, Gilead, GSK,

Hoffmann‐LaRoche, Janssen, Novartis, Pharmacyclics, Sunesis,

Verastem

B. Eichhorst

Honoraria: Hoffmann‐LaRoche, AbbVie, Celgene, Novartis, ArQule,

BeiGene, Gilead, AstraZeneca, Oxford Biomedica (UK), Adaptive

Biotechnologies

Research funding: Hoffmann‐LaRoche, AbbVie, Janssen

Y. Jiang

Employment or leadership position: Genentec Inc.

M. Hallek

Honoraria: Roche, Gilead, Mundipharma, Janssen, Celgene, Pharma-

cyclics, AbbVie

Research funding: Roche, Gilead, Mundipharma, Janssen, Celgene,

Pharmacyclics, AbbVie

K. Fischer

Honoraria: AbbVie, Hoffmann‐LaRoche

032 |CAPTIVATE PRIMARY ANALYSIS OF FIRST‐LINE

TREATMENT WITH FIXED‐DURATION IBRUTINIB PLUS

VENETOCLAX FOR CHRONIC LYMPHOCYTIC LEUKEMIA (CLL)/

SMALL LYMPHOCYTIC LYMPHOMA (SLL)

C. S. L. Tam

, J. N. Allan

, T. Siddiqi

, T. J. Kipps

, R. Jacobs

, S. Opat

P. M. Barr

, A. Tedeschi

, L. Trentin

, R. Bannerji

, S. Jackson

B. Kuss

, C. Moreno

, E. Szafer‐Glusman

, K. Russell

, C. Zhou

J. Ninomoto

, J. P. Dean

, P. Ghia

, W. G. Wierda

Peter MacCallum Cancer Center & St. Vincent's Hospital and the

University of Melbourne, Haematology and Disease Group, Melbourne,

VIC, Australia,

Weill Cornell Medicine, Hematology/Oncology, New York,

USA,

City of Hope National Medical Center, Hematology, Duarte, USA,

UCSD Moores Cancer Center, Chronic Lymphocytic Leukemia, San Diego,

USA,

Levine Cancer Institute, Hematology and Medical Oncology,

Charlotte, USA,

Monash University, Clinical Haematology, Clayton, VIC,

Australia,

Wilmot Cancer Institute, University of Rochester Medical

Center, Hematology/Oncology, Rochester, USA,

ASST Grande Ospedale

Metropolitano Niguarda, Haematology, Milan, Italy,

Hematology and

Clinical Immunology Unit, Department of Medicine, University of Padova,

Hematology, Padova, Italy,

Rutgers Cancer Institute of New Jersey,

Hematology/Oncology, New Brunswick, USA,

Middlemore Hospital,

Haematology, Auckland, New Zealand,

Flinders University and Medical

SUPPLEMENT ABSTRACTS

Centre, Haemotology and Molecular Genetics, Bedford Park, SA, Australia,

Hospital de la Santa Creu i Sant Pau, Autonomous University of

Barcelona, Hematology, Barcelona, Spain,

Pharmacyclics LLC, an

AbbVie Company, Translational Medicine, Sunnyvale, USA,

Pharmacyclics LLC, an AbbVie Company, Clinical Program

Development, Sunnyvale, USA,

Pharmacyclics LLC, an AbbVie Company,

Biostatistics, Sunnyvale, USA,

Pharmacyclics LLC, an AbbVie Company,

Oncology, Sunnyvale, USA,

Pharmacyclics LLC, an AbbVie Company,

Oncology, Sunnyvale, USA,

Division of Experimental Oncology,

Università Vita‐Salute San Raffaele and IRCCS Ospedale San Raffaele,

Experimental Oncology, Milan, Italy,

University of Texas MD Anderson

Cancer Center, Leukemia, Houston, USA

Introduction: Over two‐thirds of patients (pts) in the Minimal Re-

sidual Disease (MRD) cohort of CAPTIVATE (PCYC‐1142;

NCT02910583), a multicenter phase 2 study, achieved undetectable

MRD (uMRD) with 12 cycles of ibrutinib (I) +venetoclax (V). ≥95% of

pts were progression free at 30 mo irrespective of subsequent ran-

domized treatment (Wierda, ASH 2020). Here we present results

from the Fixed Duration (FD) cohort.

Methods: Eligible pts were aged ≤70 y and had not received

previous treatment for CLL/SLL. Pts received 3 cycles of I then 12

cycles of I+V (I 420 mg/d orally; V ramp‐up to 400 mg/d orally).

The primary endpoint was complete response (CR) rate, including

CR with incomplete recovery (CRi). Secondary endpoints were

overall response rate (ORR), duration of response, uMRD rate

(<10

–4

by 8‐color ﬂow cytometry), progression‐free survival (PFS),

overall survival (OS), tumor lysis syndrome (TLS) risk reduction,

and safety.

Results: 159 pts were enrolled. Median age was 60 y. High‐risk

genomic features included del(17p)/TP53 mutation (17%), del(11q)

(18%), complex karyotype (19%), and unmutated IGHV (56%). 92% of

pts (n =147) completed planned I treatment; 94% (n =149)

completed planned V treatment. Median time on study was 27.9 mo

(range 0.8–33.2). Overall, CR rate was 55% (95% CI 48–63); CR rate

was consistent across high‐risk subgroups. Of 88 pts who achieved a

CR; 89% of these pts (n =78) had durable CR (duration ≥1 y); 1 pt

died 7 mo after achieving a CR; 9 pts were not evaluable due to

follow‐up of <1 y. ORR was 96%. Best uMRD response was achieved

in 77% of pts in peripheral blood (PB) and 60% in bone marrow (BM).

At 24 mo, PFS rate was 95% and OS rate was 98%. Similar results

were observed in pts without del(17p) (n =136) (Table). In the 27 pts

with del(17p)/TP53 mutation, CR rate was 56%; uMRD rate was 81%

in PB and 41% in BM; PFS at 24 mo was 84% (95% CI 63–94). After I

lead‐in, 94% of pts (32/24) with high baseline TLS risk based on tu-

mor burden shifted to medium/low risk. No TLS occurred. Most

adverse events (AEs) were grade 1/2. Neutropenia (33%), hyperten-

sion (6%), and decreased neutrophil count (5%) were the most

common grade 3/4 AEs. 4% of pts discontinued I and 2% dis-

continued V due to an AE.

Conclusions: First‐line I+V is an all‐oral, once‐daily, chemotherapy‐

free, ﬁxed‐duration regimen that provides deep, durable responses

in pts with CLL/SLL, including those with high‐risk genomic features.

CR, uMRD rates, PFS, and OS appear favorable. No new safety sig-

nals were identiﬁed; the safety proﬁle of I+V was consistent with

known AEs for each agent.

EA ‐previously submitted to ASCO and EHA 2021.

The research was funded by: Pharmacyclics LLC, an AbbVie Company

Keywords: Combination Therapies, Chronic Lymphocytic Leukemia

(CLL)

Conﬂicts of interests pertinent to the abstract

C. S. L. Tam

Consultant or advisory role: Janssen, Loxo, Roche, BeiGene, AbbVie

Honoraria: Janssen, AbbVie, BeiGene, Novartis, Pharmacyclics

Research funding: Janssen, AbbVie

J. N. Allan

Consultant or advisory role: AstraZeneca, Pharmacyclics, Janssen,

BeiGene, AbbVie, Genentech, Epizyme

Honoraria: AstraZeneca, Pharmacyclics, Janssen, BeiGene, AbbVie

Research funding: Celgene, Genentech, Janssen, TG Therapeutics

T. Siddiqi

Consultant or advisory role: Juno Therapeutics, Celgene, Kite

Pharma, AstraZeneca, BeiGene

Research funding: Kite, Juno, Celgene, AstraZeneca, TG Therapeu-

tics, Oncternal, Pharmacyclics, an AbbVie Company, BeiGene

Other remuneration: Speakers bureau: AstraZeneca, Pharmacyclics,

an AbbVie Company, Janssen

SUPPLEMENT ABSTRACTS

T. J. Kipps

Employment or leadership position: Moores Cancer Center

Consultant or advisory role: AbbVie, Genentech‐Roche, Gilead,

Pharmacyclics, an AbbVie Company, Celgene, Janssen, DAVA

Oncology

Stock ownership: Oncternal Therapeutics

Honoraria: Pharmacyclics, an AbbVie Company, AbbVie, Janssen,

Celgene, Genetech, Roche, Gilead Sciences, DavaOncology

Research funding: Pharmacyclics LLC, an AbbVie Company, MD

Anderson Cancer Center, Oncternal Therapeutics Inc, Crim, Velos,

Celgene

Educational grants: AbbVie, Pharmacyclics, an AbbVie Company,

Genentech, Roche, Janssen, Gilead, Celgene, Indy Hematology Re-

view, DAVA Oncology, G‐Therapeutics, Verastem, Bionest Partners,

OncLive

Other remuneration: Speakers bureau: Verastem, Pharmacyclics, an

AbbVie Company, Janssen, AbbVie, Genentech, Gilead, DAVA Phar-

maceuticals. Patents/Royalties/Intellectual Property: Cirmtuzumab

was developed by Thomas J. Kipps

R. Jacobs

Consultant or advisory role: AbbVie, Pharmacyclics, an AbbVie

Company, AstraZeneca, Verastem

Research funding: TG Therapeutics, Pharmacyclics, an AbbVie

Company

Other remuneration: Speakers bureau: AbbVie, Pharmacyclics, an

AbbVie Company AstraZeneca, Janssen, Sanoﬁ, Genentech

S. Opat

Consultant or advisory role: Janssen, Roche, Gilead, AbbVie,

Mundipharma

Honoraria: Janssen, Roche, Gilead, AbbVie, Mundipharma

Research funding: Roche, Gilead, BeiGene, Pharmacyclics, an AbbVie

Company, AbbVie, Amgen, Janssen

P. M. Barr

Consultant or advisory role: Celgene, Pharmacyclics, an AbbVie

Company, AbbVie, Gilead, Seattle Genetics, Merck, Genentech,

Janssen, MorphoSys, AstraZeneca, TG Therapeutics

A. Tedeschi

Honoraria: Janssen, BeiGene, AstraZeneca, AbbVie

Other remuneration: Speakers bureau: Janssen, BeiGene, AstraZe-

neca, AbbVie

L. Trentin

Consultant or advisory role: AbbVie

Honoraria: Janssen, AbbVie

Research funding: Janssen

Educational grants: Roche, AbbVie, Janssen

R. Bannerji

Employment or leadership position: Sanoﬁ‐Pasteur

Research funding: Pharmacyclics, an AbbVie Company, AbbVie,

Merck & Co., Inc., Regeneron, Genentech/Roche, Triphase

S. Jackson

Consultant or advisory role: AbbVie

Educational grants: Roche

Other remuneration: Speakers bureau: AbbVie

B. Kuss

Consultant or advisory role: AbbVie, Janssen, Merck, Takeda, Kyowa

Kirin, Mundipharma, Roche Pharmaceuticals

Stock ownership: Commonwealth Serum Laboratories

Honoraria: AbbVie, Janssen, Merck, Takeda, Kyowa Kirin, Mundi-

pharma, Roche Pharmaceuticals

Other remuneration: Speakers bureau: AbbVie, Janssen, Roche

Pharmaceuticals. Expert testimony: AbbVie

C. Moreno

Consultant or advisory role: Janssen, AbbVie, AstraZeneca, BeiGene

Research funding: AbbVie, Janssen

Other remuneration: Speakers bureau: Janssen

E. Szafer‐Glusman

Employment or leadership position: AbbVie

Stock ownership: AbbVie

K. Russell

Employment or leadership position: AbbVie

Stock ownership: AbbVie

C. Zhou

Employment or leadership position: AbbVie

Stock ownership: AbbVie

J. Ninomoto

Employment or leadership position: AbbVie

Stock ownership: AbbVie, Amgen, Celgene

J. P. Dean

Employment or leadership position: Pharmacyclics LLC, an AbbVie

Company

Stock ownership: Pharmacyclics LLC, an AbbVie Company

P. Ghia

Consultant or advisory role: AbbVie, Acerta/AstraZeneca, Adaptive,

ArQule, BeiGene, Celgene/Juno, Gilead, Janssen, Lilly/Loxo, Sunesis

Honoraria: AbbVie, Acerta/AstraZeneca, Adaptive, ArQule, BeiGene,

Celgene/Juno, Gilead, Janssen, Lilly/Loxo, Sunesis

Research funding: AbbVie, Gilead, Janssen, Novartis, Sunesis

W. G. Wierda

Other remuneration: Contracted research: GSK/Novartis, Abb-

Vie, Genentech, Pharmacyclics LLC, an AbbVie Company, Acerta,

Gilead Sciences, Juno Therapeutics, KITE Pharma, Sunesis, Mira-

gen, Oncternal Therapeutics, Cyclacel, Loxo Oncology, Janssen,

Xencor

SUPPLEMENT ABSTRACTS

033 |FIRST RESULTS OF A HEAD‐TO‐HEAD TRIAL OF

ACALABRUTINIB VERSUS IBRUTINIB IN PREVIOUSLY TREATED

CHRONIC LYMPHOCYTIC LEUKEMIA

P. Hillmen

, J. C. Byrd

, P. Ghia

, A. P. Kater

, A. Chanan‐Khan

, R. R.

Furman

, S. O'Brien

, M. N. Yenerel

, A. Illes

, N. Kay

, J. A. Garcia‐

Marco

, A. Mato

, J. Pinilla‐Ibarz

, J. F Seymour

, S. Lepretre

S. Stilgenbauer

, T. Robak

, P. Patel

, K. Higgins

, S. Sohoni

W. Jurczak

St. James's University Hospital, Experimental Haematology, Leeds, UK,

The Ohio State University Comprehensive Cancer Center, Hematology,

Columbus, USA,

Università Vita‐Salute San Raffaele and IRCCS Ospedale

San Raffaele, Experimental Oncology, Milano, Italy,

Amsterdam Univer-

sity Medical Center, Amsterdam, on behalf of Hovon, Hematology, Lym-

phoma and Myeloma Research, Amsterdam, Netherlands,

Mayo Clinic

Jacksonville, Hematology, Oncology, Jacksonville, USA,

Weill Cornell

Medicine, New York Presbyterian Hospital, Hematology, Oncology, New

York, USA,

Chao Family Comprehensive Cancer Center, University of

California‐Irvine, Hematology, Oncology, Irvine, USA,

Istanbul University,

Istanbul Faculty of Medicine, Hematology, Istanbul, Turkey,

University of

Debrecen, Historical Auxiliary Sciences, Debrecen, Hungary,

Mayo Clinic

Rochester, Hematology, Rochester, USA,

Hospital Universitario Puerta

de Hierro‐Majadahonda, "Unidad de Citogenetica Molecular Servicio de

Hematologia ", Madrid, Spain,

University of Pennsylvania, Chronic

Lymphocytic Leukemia, Philadelphia, USA,

Mofﬁtt Cancer Center, Ma-

lignant Hematology, Tampa, USA,

Peter MacCallum Cancer Centre,

Royal Mselbourne Hospital, and University of Melbourne, Haematology,

Victoria, Australia,

Centre Henri Becquerel and Normandie University

UNIROUEN, Hématologie, Rouen, France,

University of Ulm, Internal

Medicine III, Haematology, Oncology, Rheumatology and Infectious Dis-

eases, Ulm, Germany,

Medican University of Lodz, Hematology, Lodz,

Poland,

AstraZeneca, Clinical Development Hematology, R&D Oncology,

South San Francisco, USA,

AstraZencea, Biostatistics, South San Fran-

cisco, USA,

AstraZeneca, Clinical Development Hematology, R&D

Oncology, South San Francisco, USA,

Maria Sklodowska‐Curie National

Research Institute of Oncology, Clinical Oncology, Krakow, Poland

Introduction: Increased selectivity of the Bruton tyrosine kinase in-

hibitor (BTKi) acalabrutinib (Aca) vs ibrutinib (Ib) may improve

tolerability. We conducted an open‐label, randomized, noninferiority,

phase 3 trial to compare Aca vs Ib in patients (pts) with chronic

lymphocytic leukemia (CLL).

Methods: Previously treated CLL pts with del(17p) or del(11q)

by central lab were randomized to receive oral Aca 100 mg

BID or Ib 420 mg QD (stratiﬁed by del(17p) status, ECOG PS [2

vs ≤1], and number of prior therapies [1–3 vs ≥4]) until pro-

gression or unacceptable toxicity. Primary endpoint was

progression‐free survival (PFS; IRC‐assessed); secondary endpoints

of all‐grade atrial ﬁbrillation (AF), grade ≥3 infection, Richter

transformation, and overall survival (OS) were assessed in hier-

archical order.

Results: 533 pts (Aca, n =268; Ib, n =265) were randomized

(median age 66 y; median 2 prior therapies; del(17p) 45.2%; del

(11q) 64.2%). At median follow‐up of 40.9 mo (range 0.0–59.1),

Aca was noninferior to Ib with median PFS of 38.4 mo in both

arms (HR 1.00; 95% CI 0.79–1.27). Aca was statistically superior to

Ib in all‐grade AF incidence (9.4% vs 16.0%; P=0.023). Among

other secondary endpoints, grade ≥3 infection (Aca: 30.8%, Ib:

30.0%) and Richter transformation (Aca: 3.8%, Ib: 4.9%) were

comparable between arms. Median OS was not reached in either

arm (HR 0.82 [95% CI 0.59–1.15]), with 63 (23.5%) deaths in the

Aca arm and 73 (27.5%) in the Ib arm. Among any‐grade AEs in

≥20% of pts in either arm, Aca had lower incidence of hyperten-

sion (9.4%, 23.2%), arthralgia (15.8%, 22.8%), and diarrhea (34.6%,

46.0%) but higher incidence of headache (34.6%, 20.2%) and cough

(28.9%, 21.3%). AEs led to treatment discontinuation in 14.7% of

Aca‐vs 21.3% of Ib‐treated pts. Among any‐grade events of clin-

ical interest, cardiac, hypertension, and bleeding events were less

frequent with Aca (Table).

Conclusions: In this ﬁrst head‐to‐head trial of BTKis in CLL, Aca

demonstrated non‐inferior PFS with less cardiotoxicity and fewer

discontinuations due to AEs vs Ib.

EA ‐previously submitted to ASCO and EHA 2021.

TABLE 1Selected events of clinical interest

SUPPLEMENT ABSTRACTS

The research was funded by: Acerta Pharma, a member of the

AstraZeneca Group

Keywords: Chronic Lymphocytic Leukemia (CLL)

Conﬂicts of interests pertinent to the abstract

P. Hillmen

Consultant or advisory role: Janssen, Abbvie, AstraZeneca, Apellis

Honoraria: Janssen, Abbvie, Roche, AstraZeneca, Apellis

Research funding: Janssen, AbbVie, Roche, Pharmacyclics, Gilead

Educational grants: Janssen, Abbvie

J. C. Byrd

Employment or leadership position: Vincerx

Consultant or advisory role: Vincerx, Astrazeneca, Trillium, Novartis

Stock ownership: Vincerx

Honoraria: Syndax, Novartis, AstraZeneca, Trillium

Research funding: AstraZeneca

Other remuneration: several patents with small molecules unrelated

to this research

P. Ghia

Consultant or advisory role: AbbVie, AstraZeneca, ArQule/MSD,

BeiGene, Celgene/Juno/BMS, Gilead, Janssen, Lilly/loxo

Honoraria: AbbVie, AstraZeneca, ArQule/MSD, BeiGene, Celgene/

Juno/BMS, Gilead, Janssen, Lilly/loxo

Research funding: AbbVie, Gilead, Janssen, Novartis, Sunesis

A. P. Kater

Consultant or advisory role: Abbvie, Genentech, Janssen, Astra Zeneca

Honoraria: Abbvie, Genentech, Janssen, Astra Zeneca

Research funding: Abbvie, Genentech, Janssen, Astra Zeneca. BMS,

Celgene

Educational grants: Abbvie, Genentech, Janssen, Astra Zeneca

A. Chanan‐Khan

Research funding: AstraZeneca

R. R. Furman

Consultant or advisory role: Pharmacyclics, Janssen Biotech, Gen-

entech/Roche, Loxo, TG Therapeutics, Verastem, Acerta Pharma,

AstraZeneca, Beigene, Incyte, OncoTracker, AbbVie, MorphoSys, Sanoﬁ

Research funding: Acerta Pharma, TG Therapeutics; Honoraria:

Janssen, AstraZeneca

Educational grants: TG Therapeutics, Janssen Oncology

Other remuneration: Expert Testimony: AbbVie, Janssen Oncology;

Other: Incyte, Janssen Biotech

S. O'Brien

Consultant or advisory role: Gilead, Pharmacylics, TG Therapeutics,

Pﬁzer, Sunesis. Amgen, Astellas, Celgene, GSK, Janssen Oncology,

Aptose Biosciences Inc, Vaniam Group LLC, AbbVie, Alexion, Vera-

stem, Eisai, Juno Therapeutics, Vida Ventures, Autolus, Johnson and

Johnson, Merck, BMS

Research funding: Kite Regeneron, Acerta Pharma, Gilead, Pharma-

cylics, TG Therapeutics, Pﬁzer, Sunesis

M. N. Yenerel

Honoraria: Johnson and Johnson

Educational grants: Johnson and Johnson

A. Illes

Consultant or advisory role: Janssen, Celgene, Novartis, Pﬁzer,

Takeda, Roche

Research funding: Takeda, Seattle Genetics

Educational grants: Novartis, Janssen, Pﬁzer, Roche

N. Kay

Consultant or advisory role: MorphoSys, Celgene, Agios, CyomX

Therapeutics, AstraZeneca, Pharmacyclics, DAVA Pharmaceuticals,

June Therapeutics, Rigel, Oncotracker, BMS, AbbVie, Targeted

Oncology, Acerta Pharma, MEI Pharma, Sunesis Pharmaceuticals, TG

Therapeutics, Tolero Pharmaceuticals

Research funding: Pharmacyclics/Janssen, Tolero Pharmaceuticals,

Acerta Pharma, MEI Pharma, Celgene, Genentech, Sunesis Pharma-

ceuticals, AbbVie, TG Therapeutics, BMS

J. A. Garcia‐Marco

Consultant or advisory role: AbbVie, Janssen, Speakers Bureau:

AbbVie, Janseen, Roche

Research funding: Janssen

A. Mato

Consultant or advisory role: TG Therpeutics, AbbVie/Genentech,

Celgene, Adaptive Biotechnologies, Pharmacyclics, Verastem, John-

son and Johnson, Acerta Pharma, AstraZeneca, DTRM, Loxo/Lilly,

Curio, Merck, BMS/Pﬁzer

Research funding: Regeneron, TG Therpeutics, Sunesis Pharmaceu-

ticals, LOXO, AbbVie/Genentech, Pharmacyclics, Adaptive Bio-

technologies, Johnson and Johnson, Acerta Pharma, AstraZeneca,

DTRM, Genmab, Nurix

J. Pinilla‐Ibarz

Consultant or advisory role: Abbvie, Janssen, AstraZeneca, Novartis,

TG therapeutics, Takeda

Honoraria: Abbvie, Janssen, Takeda, AstraZeneca, Pharmacyclics,

Sanoﬁ

Research funding: MEI, Sunesis

Other remuneration: Speaker's Bureau: Abbvie, Janssen, Astraze-

neca, Takeda

J. F. Seymour

Consultant or advisory role: AbbVie, Amgen, AstraZeneca, Celgene,

Gilead, GSK, Hoffmann La‐Roche, Janssen, Novartis

Honoraria: AbbVie, Amgen, AstraZeneca, Celgene, Gilead, GSK,

Hoffmann La‐Roche, Janssen, Novartis

Research funding: AbbVie, Amgen, AstraZeneca, Celgene, Gilead,

GSK, Hoffmann La‐Roche, Janssen, Novartis

Educational grants: AbbVie, Amgen, AstraZeneca, Celgene, Gilead,

GSK, Hoffmann La‐Roche, Janssen, Novartis

Other remuneration: Speakers Bureau: AbbVie, Amgen, AstraZeneca,

Celgene, Gilead, GSK, Hoffmann La‐Roche, Janssen, Novartis

SUPPLEMENT ABSTRACTS

S. Stilgenbauer

Consultant or advisory role: AbbVie, Amgen, AstraZeneca, Celgene,

Gilead, GSK, Hoffmann La‐Roche, Janssen, Novartis

Honoraria: AbbVie, Amgen, AstraZeneca, Celgene, Gilead, GSK,

Hoffmann La‐Roche, Janssen, Novartis

Research funding: AbbVie, Amgen, AstraZeneca, Celgene, Gilead,

GSK, Hoffmann La‐Roche, Janssen, Novartis

Educational grants: AbbVie, Amgen, AstraZeneca, Celgene, Gilead,

GSK, Hoffmann La‐Roche, Janssen, Novartis

Other remuneration: Speakers Bureau: AbbVie, Amgen, AstraZeneca,

Celgene, Gilead, GSK, Hoffmann La‐Roche, Janssen, Novartis

T. Robak

Consultant or advisory role: Sandoz, Takeda, Momenta

Research funding: Acerta Pharma, Roche, Janssen, AbbVie, Novartis,

BioGene, AstraZeneca, Pharmacyclics, UCB, Pﬁzer, Morphosys, UTX‐

TGR, GSK, Bristol Myers Squibb

Educational grants: Roche, Janssen, AbbVie; Honoraria: Sandoz, UCB,

Novartis, Octapharma, BioGene, AstraZeneca, Pharmacyclics

P. Patel

Employment or leadership position: AstraZeneca

Stock ownership: AstraZeneca

K. Higgins

Employment or leadership position: AstraZeneca, PROMETRIKA, LLC

S. Sohoni

Employment or leadership position: AstraZeneca

Stock ownership: Theravance

W. Jurczak

Consultant or advisory role: Mei pharma, Debiopharm, Loxo, Takeda,

Astra Zeneca, Beigene

Research funding: GSK, Acerta, Astra Zeneca, Beigene, Nordic

Nanovector, Incyte, Debiopharm, Incyte, Genenthech, Janssen, Loxo,

Mei Pharma, Morphosys, Takeda, TG Therapeutics

034 |BENDAMUSTINE, FOLLOWED BY OBINUTUZUMAB,

ACALABRUTINIB AND VENETOCLAX IN PATIENTS (PTS) WITH

RELAPSED/REFRACTORY CHRONIC LYMPHOCYTIC LEUKEMIA

(CLL): CLL2‐BAAG TRIAL OF THE GCLLSG

P. Cramer

, M. Fürstenau

, S. Robrecht

, A. Giza

, A. M. Fink

K. Fischer

, P. Langerbeins

, O. Al Sawaf

, E. Tausch

, C. Schneider

J. Schetelig

, P. Dreger

, S. Böttcher

, K. A. Kreuzer

, A. Schilhabel

M. Brüggemann

, M. Kneba

, C. M. Wendtner

, S. Stilgenbauer

B. Eichhorst

, M. Hallek

University of Cologne, Faculty of Medicine and University Hospital of

Cologne, Department I of Internal Medicine and German CLL Study

Group; Center for Integrated Oncology Aachen Bonn Cologne

Duesseldorf (CIO ABCD), Cologne, Germany,

University Hospital Ulm,

Department III of Internal Medicine, Ulm, Germany,

University

Hospital Carl Gustav Carus, Department I of Internal Medicine,

Dresden, Germany,

University Hospital Heidelberg, Department V of

Internal Medicine, Heidelberg, Germany,

University Hospital Rostock,

Department III of Internal Medicine, Rostock, Germany,

University of

Schleswig‐Holstein, Campus Kiel, Department II of Internal Medicine,

Kiel, Germany,

Klinikum Schwabing, Department of Hematology,

Oncology, Immunology, Palliative Care, Infectious Diseases and Tropical

Medicine, Munich, Germany

Introduction: The CLL2‐BAG trial had shown very favourable

response and minimal residual disease (MRD) rates with a sequential

treatment consisting of an optional bendamustine (B) debulking,

followed by a doublet combination of obinutuzumab (G) and ven-

etoclax (V) [Cramer et al, Lancet Oncol. 2018]. Following these re-

sults, the triplet combination adding the BTK inhibitor (BTK‐I)

acalabrutinib (A) was tested in the CLL2‐BAAG trial to further

improve efﬁcacy.

Methods: An optional debulking with 2 cycles of B was recommended

in pts with lymphocyte counts ≥25.000/µl and/or lymph nodes ≥5cm

(70mg/m

d1&2 q28 days). In the induction, G (1000mg) was

administered 3 times in cycle 1 (days 1/2, 8 & 15) and every 4 weeks

in cycles 2‐6. A (100mg bid) was added in cycle 2 followed by V in

cycle 3 with a dose ramp‐up (to 400mg daily) over 5 weeks. In the

maintenance therapy, A and V remained unchanged while intervals of

G were increased to 3 months.

The primary endpoint was the rate of undetectable MRD (uMRD) in

PB at the end of induction therapy (deﬁned as <10‐4 by ﬂow

cytometry, assessed centrally). Sample size was estimated with the

objective to test against the null hypothesis of ≤70% using a one‐

sided one‐sample binomial test on the basis of an assumed

improvement of uMRD rate to ≥90%. Secondary endpoints included

iwCLL responses, safety and survival parameters.

Results: Between January 2019 and June 2020, 46 pts were enrolled,

1 pt with a violation of inclusion/exclusion criteria and ≤2 induction

cycles was excluded from the analysis. The 45 evaluable pts had

relapsed/refractory (r/r) CLL with a median of one prior therapy

(range 1‐4), 21 pts (47%) had already received a targeted agent,

including 8 pts with a BTK‐I, 7 pts with V‐based therapies, 3 pts with

both and 3 pts with idelalisib. Fourteen pts (32%) had a del(17p)/

TP53 mutation, 34 (76%) had an unmutated IGHV status and 12

(30%) a complex karyotype.

18 pts (40%) received B debulking, 27 (60%) pts immediately started

with the induction with G, A and V. 44 pts (98%) received 6 induction

cycles and 32 pts (71%) have thus far started with the maintenance

treatment.

At the end of the induction all pts responded, 8 pts (18%) had a CR/

CRi and 37 pts (82%) a PR. With an uMRD rate in PB of 76% (34 pts),

the primary endpoint was not met (95% CI 61%‐87%, p =0.258).

As of February 25th 2021, 430 adverse events (AEs) were reported,

including 29 SAEs (7%) and 69 AEs (16%) of CTC°3‐4. Most common

were gastrointestinal AEs, cytopenias and infections.

Conclusion: Sequential treatment with B debulking, followed by the

triplet combination of G, A and V was well tolerated. Although the

SUPPLEMENT ABSTRACTS

primary endpoint was not met with given sample size, the ORR of

100% and a rate of uMRD of 76% in PB at the end of induction phase

compare favourably to other regimens for r/r CLL. The lower uMRD

rate may be explained by the redistribution phenomenon caused by

BTK‐I and could improve with continued maintenance treatment in

the long run.

The research was funded by: The research (IIT study) was funded by

AstraZeneca and F. Hoffmann‐LaRoche.

Keywords: Chronic Lymphocytic Leukemia (CLL), Molecular Targeted

Therapies, Combination Therapies

Conﬂicts of interests pertinent to the abstract

P. Cramer

Consultant or advisory role: AbbVie and AstraZeneca

Honoraria: AbbVie, AstraZeneca, F. Hoffmann‐LaRoche and Janssen‐

Cilag

Research funding: Acerta, AstraZeneca, Beigene, F. Hoffmann‐

LaRoche, Gilead, Janssen‐Cilag and Novartis

Educational grants: AbbVie, AstraZeneca, F. Hoffmann LaRoche, and

Janssen‐Cilag

A. M. Fink

Honoraria: Janssen

Research funding: Celgene

Educational grants: Abbvie

K. Fischer

Honoraria: AbbVie and F. Hoffmann‐LaRoche

Educational grants: F. Hoffmann‐LaRoche

P. Langerbeins

Honoraria: AbbVie, F. Hoffmann‐LaRoche and Janssen‐Cilag

Research funding: Janssen‐Cilag

Educational grants: AbbVie, F. Hoffmann‐LaRoche and Janssen‐Cilag

O. Al Sawaf

Consultant or advisory role: AbbVie, AstraZeneca, Janssen, Gilead

and Roche

Honoraria: AbbVie, AstraZeneca, Janssen, Gilead and Roche

Research funding: AbbVie, BeiGene, Janssen and Roche

Educational grants: AbbVie, AstraZeneca, Janssen, Gilead and

Roche

E. Tausch

Consultant or advisory role: AbbVie, Janssen‐Cilag, Roche

Honoraria: AbbVie, Janssen‐Cilag, Roche

Research funding: AbbVie, Janssen‐Cilag, Roche

J. Schetelig

Consultant or advisory role: AbbVie, AstzaZeneca, Janssen, Roche,

and Gilead

Honoraria: AbbVie, AstzaZeneca, Janssen, Roche, and Gilead

P. Dreger

Consultant or advisory role: AbbVie, AstraZeneca, bluebird bio,

Gilead, Janssen, Novartis, Riemser, Roche

Honoraria: AbbVie, AstraZeneca, Gilead, Novartis, Riemser, Roche

Research funding: Riemser

S. Böttcher

Honoraria: Roche, AbbVie, Becton Dickinson, Janssen, Astra‐Zeneca,

Sanoﬁ.

Research funding: Janssen‐Cilag

K. A. Kreuzer

Consultant or advisory role: AbbVie, Amgen, F. Hoffmann‐LaRoche,

Gilead, Janssen‐Cilag and Mundipharma

Honoraria: AbbVie, Amgen, F. Hoffmann‐LaRoche, Gilead, Janssen‐

Cilag and Mundipharma

Research funding: AbbVie, Amgen, F. Hoffmann‐LaRoche, Gilead,

Janssen‐Cilag and Mundipharma

M. Brüggemann

Consultant or advisory role: Afﬁmed, Amgen, Incyte, Janssen,

Regeneron

Honoraria: Afﬁmed, Amgen, Incyte, Janssen, Regeneron

Research funding: Afﬁmed, Amgen, Incyte, Janssen, Regeneron

Educational grants: Afﬁmed, Amgen, Incyte, Janssen, Regeneron

Other remuneration: none

C. M. Wendtner

Consultant or advisory role: AbbVie, Hoffmann‐LaRoche, Genentech,

Gilead, GlaxoSmithKline, Janssen‐Cilag, Mundipharma and

Pharmacyclics

Honoraria: AbbVie, Hoffmann‐LaRoche, Genentech, Gilead, Glax-

oSmithKline, Janssen‐Cilag, Mundipharma and Pharmacyclics

Research funding: AbbVie, Hoffmann‐LaRoche, Genentech,

Gilead, GlaxoSmithKline, Janssen‐Cilag, Mundipharma and

Pharmacyclics

Educational grants: AbbVie, Hoffmann‐LaRoche, Genentech,

Gilead, GlaxoSmithKline, Janssen‐Cilag, Mundipharma and

Pharmacyclics

S. Stilgenbauer

Consultant or advisory role: AbbVie, Amgen, Boehringer‐Ingelheim,

Celgene, F. Hoffmann‐LaRoche, Genentech, Genzyme, Gilead, Glax-

oSmithKline, Janssen‐Cilag, Mundipharma, Novartis and

Pharmacyclics

Honoraria: AbbVie, Amgen, Boehringer‐Ingelheim, Celgene,

F. Hoffmann‐LaRoche, Genentech, Genzyme, Gilead, GlaxoSmithK-

line, Janssen‐Cilag, Mundipharma, Novartis and Pharmacyclics

Research funding: AbbVie, Amgen, Boehringer‐Ingelheim, Celgene, F.

Hoffmann‐LaRoche, Genentech, Genzyme, Gilead, GlaxoSmithKline,

Janssen‐Cilag, Mundipharma, Novartis and Pharmacyclics

Educational grants: AbbVie, Amgen, Boehringer‐Ingelheim, Celgene, F.

Hoffmann‐LaRoche, Genentech, Genzyme, Gilead, GlaxoSmithKline,

Janssen‐Cilag, Mundipharma, Novartis and Pharmacyclics

B. Eichhorst

Consultant or advisory role: AbbVie, AstraZeneca, Celgene, F.

Hoffmann‐LaRoche, Gilead, Janssen‐Cilag

SUPPLEMENT ABSTRACTS

Research funding: AbbVie, AstraZeneca, Celgene, F. Hoffmann‐

LaRoche, Gilead, Janssen‐Cilag

Educational grants: AbbVie, AstraZeneca, Celgene, F. Hoffmann‐

LaRoche, Gilead, Janssen‐Cilag

M. Hallek

Consultant or advisory role: AbbVie, Amgen, Celgene, F. Hoffmann‐

LaRoche, Gilead, Janssen‐Cilag and Mundipharma

Honoraria: AbbVie, Amgen, Celgene, F. Hoffmann‐LaRoche, Gilead,

Janssen‐Cilag and Mundipharma

Research funding: AbbVie, Amgen, Celgene, F. Hoffmann‐LaRoche,

Gilead, Janssen‐Cilag and Mundipharma

SESSION 5: PEDIATRIC LYMPHOMAS

035 |CURRENT STATUS AND CHALLENGES IN DIAGNOSIS OF

CHILDHOOD NHL

W. Klapper

Institute of Pathology, Hematopathology Section, University Hospital

Schleswig‐Holstein, Kiel, Germany

Over the last decades sequencing technology gave insight into

details of the molecular‐genetic landscape and has changed deﬁ-

nitions of B‐and T‐cell lymphomas as well as inroduction of new

subtypes. Moreover, molecular testing has become a standard

proceedure in diagnostic pathology. Pediatric oncologist are facing

two major challenges. First, the vast majority of studies on new

diagnostic markers and subtypes of lymphomas have been con-

ducted in adult but patients only and second, most genetic data

derived from sequencing studies are neither of diagnostic nor of

predictive of prognostic use in pediatric patients. For clinicians and

pathologist it is a challenge is to sort out what information is

required to obtain optimal diagnostic certainty in a child suffering

from lymphoma. In this session, I will present a case‐based lecture

to discuss if diagnostic standards can be deﬁned for the most

frequent Non‐Hodgkin lymphomas lymphomas in children and

adults with a speciﬁc focus on the differences to adults. I will

discuss that the major challenges in the diagnosis of lymphomas in

children and adolescents are probably not related to molecular

testing but to issues that appear trivial at a ﬁrst glance such as

availability of sufﬁcient biopsy material, clinical information, his-

topathological experience and a rational but limited testing strat-

egy unsing immunohistochemistry and molecular testing. In fact it

seems that despite tremendous progress in molecular insights

into lymphoma biology, for the most frequent entities of Non‐

Hodgkin lymphoma in young patients the requirements for diag-

nosis leading to optimal patient care are vastly unaltered over the

last decades.

Keywords: Non‐Hodgkin (Pediatric, Adolescent, and Young

Adult)

Conﬂicts of interests pertinent to the abstract

W. Klapper

Consultant or advisory role: Takeda

Research funding: Takeda, Amgen, Regeneron

036 |DOSE‐ADJUSTED EPOCH‐RITUXIMAB OR INTENSIFIED

B‐NHL‐BFM‐TYPE THERAPY FOR PEDIATRIC PRIMARY

MEDIASTINAL B‐CELL LYMPHOMA

F. Knörr

, M. Zimmermann

, A. Attarbaschi

, E. Kabíčková

, B.

Maecker‐Kolhoff

, S. Ruf

, I. Kühnle

, M. Ebinger

, A.‐K. Garthe

I. Oschlies

, W. Klapper

, B. Burkhardt

, W. Wößmann

UKE, Departement of Pediatric Hematology and Oncology, Hamburg,

Germany,

Hannover Medical School, Clinic for Pediatric Hematology and

Oncology, Hannover, Germany,

St. Anna Children's Hospital, Medical

University of Vienna, Department of Pediatric Hematology and Oncology,

Vienna, Austria,

University of Prague, Department for Paediatric

Haematology and Oncology, Prague, Czech Republic,

University of

Gießen, Pediatric Hematology and Oncology, Gießen, Germany,

University Medical Center Göttingen, Division of Pediatric Hematology

and Oncology, Göttingen, Germany,

University of Tübingen, Department

of Pediatric Hematology and Oncology, Tübingen, Germany,

University‐

Hospital of Münster, Pediatric Hematology and Oncology, Münster,

Germany,

Universitätsklinikum Schleswig‐Holstein, Campus Kiel, Insti-

tute of Pathology, Hematopathology Section and Lymph Node Registry,

Kiel, Germany

Introduction: There is no standard therapy for children and ado-

lescents with primary mediastinal large B‐cell lymphoma (PMBCL).

Relapse rates reach up to 40% with chemotherapy regimen

designed for treatment of mature B‐NHL in children. Therefore,

treatment for children and adolescents was intensiﬁed in the B‐

NHL BFM 04 trial (B 04). Dose‐adjusted chemo‐immunotherapy

with etoposide, prednisone, cyclophosphamide, doxorubicin and

rituximab (DA‐EPOCH‐R) has been reported as an alternative,

effective treatment strategy in adults and few children and was

subsequently introduced as treatment recommendation by the

NHL‐BFM study group.

Methods: Treatment for PMBCL in the B 04 trial (2004 – 2010) was

stratiﬁed by initial LDH values and intensiﬁed from the previous

NHL‐BFM 95 trial (N 95) by adding two treatment courses. The

infusion time of MTX in B 04 was 24 hours for all patients, while it

was 4 hours for 7/20 patients in N 95. From 2010 onward, patients

with PMBCL in the B 04 trial and the NHL‐BFM registry 2012

received DA‐EPOCH‐R. The recommendation was modiﬁed from the

original protocol by the limitation of the cumulative dose of doxo-

rubicin to 360 mg/m

and the application of at least one dose of

intrathecal chemotherapy.

We compared the efﬁcacy of DA‐EPOCH‐R (n =67, 52 without 1‐2

courses BFM‐type pretreatment) and intensiﬁed BFM‐type chemo-

therapy for mature B‐NHL (n =29) for children and adolescents with

PMBCL included in the B 04 trial and the NHL‐BFM registry 2012 to

the previous treatment strategy of the N 95 trial (n =20).

SUPPLEMENT ABSTRACTS

Results: Two patients were excluded because they received

different treatment. The median age of 116 patients was 16.2

years, 53% were female. For treatment with DA‐EPOCH‐R, B 04

and N 95, event‐free (EFS) survival at 5 years was 84% (95%‐

conﬁdence interval (CI), 72 – 91%), 59% (CI, 39 – 74%), and 39%

(CI, 23 – 65%); survival (OS) was 90% (CI, 79 – 95%), 72% (CI, 51

– 88%) and 70% (CI, 45 – 85%), respectively. EFS and OS

with DA‐EPOCH‐R were signiﬁcant superior to treatment with B

04 (p =.016 for EFS, p =.039 for OS) and N 95 (p <.001 for EFS

and p =.026 for OS). The difference in EFS observed be-

tween intensiﬁed B‐NHL‐BFM 04 and the previous treatment

regimen was not signiﬁcant (p =.14). EFS for 52 patients receiving

DA‐EPOCH‐R without pretreatment was 87% (CI, 74 – 93%).

CNS was involved at relapse in four of 11 patients relapsing af-

ter DA‐EPOCH‐R in contrast to none of 22 after BFM‐type B‐

NHL‐therapy (p =.008). Except for younger age at diagnosis,

no risk factor for treatment failure with DA‐EPOCH‐R was

identiﬁed.

Conclusion: DA‐EPOCH‐R was superior to the previous

chemotherapy regimens for mature B‐NHL in children and ado-

lescents with PMBCL. The observed improvement in EFS with

intensiﬁed chemotherapy in the B 04 trial was not statistically

signiﬁcant. A possibly higher risk for CNS relapse with DA‐

EPOCH‐R needs to be addressed in future collaborative clinical

trials.

EA ‐previously submitted to regional or national meetings (up to

1000 attendees)

Keywords: Non‐Hodgkin (Pediatric, Adolescent, and Young Adult),

Combination Therapies

No conﬂicts of interests pertinent to the abstract.

037 |AN OPEN‐LABEL, PHASE 1/2 STUDY OF FRONTLINE

BRENTUXIMAB VEDOTIN +ADRIAMYCIN, VINBLASTINE, AND

DACARBAZINE IN PAEDIATRIC PATIENTS WITH ADVANCED

STAGE HODGKIN LYMPHOMA

A. R. K. Franklin

, F. A. V. Luisi

, M. A. Pianovski

, M. A. Salvino

F. Fagioli

, S. Epelman

, L. B De Abreu Lima

, R. E. Norris

, V. Odone‐

Filho

, M. Zecca

, C. Favre

, R. Kobayashi

, Y. Sidi

, F. Campana

E. J. Leonard

, F. Locatelli

Children's Hospital Colorado, Center for Cancer and Blood Disorders,

Aurora, Colorado, USA,

GRAACC/UNIFESP, Pediatria, São Paulo,

Brazil,

Erastinho Hospital (previously Erasto Gaertner Hospital),

Pediatric Oncology, Curitiba, Brazil,

IDOR, Salvador, Hospital Sao

Rafael, Hematology, Salvador, Brazil,

Regina Margherita Children's

Hospital, Department of Sciences of Public Health and Pediatrics, Turin,

Italy,

Hospital Santa Marcelina, Pediatric Oncology, São Paulo, Brazil,

INCA ‐Instituto Nacional de Câncer, Hematology, Rio de Janeiro,

Brazil,

Cincinnati Childrens Hospital Medical Center, Cancer and Blood

Diseases Institute, Department of Pediatrics, Cincinnati, Ohio, USA,

ITACI – Instituto De Tratamento Do Câncer Infantil, Faculdade De

Medicina Da Universidade De São Paulo, Departament De Pediatria,

São Paulo, Brazil,

Fondazione IRCCS Policlinico San Matteo, Pediatric

Hematology / Oncology, Pavia, Italy,

Azienda Ospedaliero

Universitaria Ospedale Pediatrico Meyer, Dipartimento di

Oncoematologia, Firenze, Italy,

Sapporo Hokuyu Hospital, Department

of Hematology/Oncology for Children and Adolescents, Sapporo, Japan,

Millennium Pharmaceuticals Inc., Cambridge, MA, USA, a wholly

owned subsidiary of Takeda Pharmaceutical Company Limited,

Statistics and Quantitative Sciences, Cambridge, Massachusetts, USA,

Millennium Pharmaceuticals Inc., Cambridge, MA, USA, a wholly

owned subsidiary of Takeda Pharmaceutical Company Limited,

Kaplan‐Meier estimates of event free survival (EFS) by treatment for pediatric PMBCL

SUPPLEMENT ABSTRACTS

Department Clinical Sciences ‐OTAU, Cambridge, Massachusetts, USA,

IRCCS Ospedale Pediatrico Bambino Gesù, Pediatric Hematology/

Oncology, Rome, Italy

Introduction: Paediatric Hodgkin lymphoma (HL) has high

cure rates, but in younger patients (pts) multiagent regimens are

associated with serious sequelae from radiation and alkylating

chemotherapy including: increased secondary malignancies,

cardiovascular disease, hypothyroidism, infertility, pulmonary

diseases, and infections. C25004 (NCT02979522) is a Phase (Ph)

1/2 open‐label study to assess the safety and efﬁcacy of frontline

brentuximab vedotin +adriamycin, vinblastine, and dacarbazine

(A+AVD) in paediatric pts with advanced‐stage, classical

HL (cHL).

Methods: Eligible pts were aged 5 to <18 years, had untreated

stage III/IV cHL, Lansky/Karnofsky Performance Status (LKPS) ≥50,

and bidimensional measurable disease by radiography. In Ph1, pts

received up to 6 28‐day cycles of A+AVD on days 1 and 15 of

each cycle, with brentuximab vedotin given as a 36 mg/m

or 48

mg/m

dose. Toxicity was evaluated per National Cancer Institute

Common Terminology Criteria for Adverse Events, v4.03. Ph 1

primary objectives were to assess safety and tolerability and to

identify the recommended Ph2 dose (RP2D) of brentuximab

vedotin. Ph2 primary objectives were to assess the objective

response rate (ORR) (complete [CR] +partial remission [PR] rates),

and to determine the proportion of pts achieving PET‐negativity

(Deauville score 1–3) after 2 cycles (PET2‐), and the proportion

of pts completing 6 cycles of therapy at the RP2D. The percentage

of pts receiving radiotherapy (RT) after study treatment and the

safety and tolerability of A+AVD were included as Ph2 secondary

endpoints.

Results: In total, 59 pts were enrolled (Ph1 n =8, Ph2 n =51),

median age was 14 years (range 6–17), 53% were male and me-

dian LKPS was 90.0 (range 70–100). RP2D was 48 mg/m

as re-

ported by Franklin et al. (ASH 2018, abstract 1644); all pts

received 6 cycles of A+AVD. Ph 1/2 results for the total popula-

tion (N =59) are reported hereafter. ORR per independent review

facility at end of treatment was 88% (95% CI: 77, 95), 76% of pts

(95% CI: 63, 86) achieved a CR. PET2‐rate was 90% (95% CI: 79,

96). After 17.31 months (median) follow‐up 13 pts (22%) had

progressive disease. Safety data are summarised in the Table. The

most common any‐grade treatment‐emergent adverse events

(TEAEs) were vomiting (85%) nausea (75%), and neutropenia

(58%); 41% of pts experienced serious AEs (SAEs). There were no

on‐study deaths.

Conclusions: Frontline brentuximab vedotin (48 mg/m

)+AVD was

well tolerated providing high rates of ORR, CR, and PET2‐in paedi-

atric pts with advanced cHL, aligning with adult efﬁcacy and safety

seen in ECHELON‐1. Patients continue in follow‐up.

The research was funded by: Millennium Pharmaceuticals, Inc.,

Cambridge, MA, USA, a wholly owned subsidiary of Takeda Phar-

maceutical Company Limited.

Keywords: Hodgkin lymphoma, Molecular Targeted Therapies

Conﬂicts of interests pertinent to the abstract

F. A. V. Luisi

Employment or leadership position: GRAACC

Honoraria: GRAACC

M. A. Pianovski

Research funding: Millennium Pharmaceuticals, Inc., Cambridge, MA,

USA, a wholly owned subsidiary of Takeda Pharmaceutical Company

Limited

M. A. Salvino

Consultant or advisory role: Takeda Advisory Board

Research funding: Brentuximab Clinical Trials HSR PI

R. E. Norris

Employment or leadership position: Merck Pharmaceuticals

Educational grants: Merck Pharmaceuticals

SUPPLEMENT ABSTRACTS

M. Zecca

Consultant or advisory role: AMGEN, Bluebird, MEDAC

Educational grants: JAZZ Pharmaceuticals

Y. Sidi

Employment or leadership position: Millennium Pharmaceuticals Inc.,

Cambridge, MA, USA, a wholly owned subsidiary of Takeda Phar-

maceutical Company Limited

F. Campana

Employment or leadership position: Millennium Pharmaceuticals Inc.,

Cambridge, MA, USA, a wholly owned subsidiary of Takeda Phar-

maceutical Company Limited

E. J. Leonard

Employment or leadership position: Millennium Pharmaceuticals Inc.,

Cambridge, MA, USA, a wholly owned subsidiary of Takeda Phar-

maceutical Company Limited

Stock ownership: Millennium Pharmaceuticals Inc., Cambridge, MA,

USA, a wholly owned subsidiary of Takeda Pharmaceutical Company

Limited

038 |BRENTUXIMAB VEDOTIN WITH CHEMOTHERAPY IN

ADOLESCENTS AND YOUNG ADULTS (AYAS) WITH STAGE III OR

IV HODGKIN LYMPHOMA: A SUBGROUP ANALYSIS FROM THE

PHASE 3 ECHELON‐1 STUDY

H. E. Crosswell

, A. S. LaCasce

, N. L. Bartlett

, D. J. Straus

K. J. Savage

, P. L. Zinzani

, G. P. Collins

, M. A. Fanale

, K. Fenton

C. Dong

, H. H. Miao

, A. P. Grigg

Bon Secours Hematology Oncology, Bon Secours, St. Francis Health

System, Greenville, South Carolina, USA,

Dana‐Farber Cancer Institute,

Partners CancerCare, Boston, Massachusetts, USA,

Siteman Cancer

Center, Washington University School of Medicine, St. Louis, Missouri,

USA,

Lymphoma Service, Department of Medicine, Memorial Sloan Ket-

tering Cancer Center, New York, New York, USA,

BC, Cancer, Vancouver,

Canada,

Institute of Hematology “L. e A. Seràgnoli”, University of

Bologna, Bologna, Italy,

Oxford University Hospitals, NHS Trust, Oxford,

UK,

Medical Affairs, Seagen Inc., Bothell, Washington, USA,

Biostatistics,

Seagen Inc., Bothell, Washington, USA,

Takeda, Oncology, Cambridge,

Massachusetts, USA,

Takeda, Oncology, Cambridge, Massachusetts,

USA,

Department of Clinical Haematology, Austin Hospital, Austin, VIC,

Australia

Background: Classical hodgkin lymphoma (cHL) is a rare disease

that commonly occurs in adolescents and young adults (AYAs),

typically deﬁned as 15 to 39 years. Given their young age at

presentation, key factors in treatment selection include not only a

high cure rate, but minimal long‐term toxicities. Brentuximab

vedotin is a CD30‐directed ADC approved in combination with

doxorubicin, vinblastine, and dacarbazine chemotherapy (A+AVD)

for adults with previously untreated stage III/IV cHL based on

results from the phase 3 ECHELON‐1 trial. Recent 5‐year data

demonstrated a signiﬁcantly improved PFS per investigator (INV)

vs doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD)

(HR, 0.69; 95% CI, 0.54–0.9; P =0.003) (Straus 2020). Here we

describe the key efﬁcacy and safety results for AYA pts enrolled in

ECHELON‐1.

Methods: ECHELON‐1 (N =1334) is a global, open‐label, multi-

center, randomized trial of pts with previously untreated stage III/IV

cHL. A total of 771 AYAs (58%) received either A+AVD (n =396) or

ABVD (n =375) with a PET scan after cycle 2 (PET2). An analysis of

PFS (time from randomization to progression or death from any

cause) per INV was conducted.

Results: These results refer to the AYA subset. After a median

follow‐up of 60.7 months (95% CI, 60.4‐61.0), there was a 36%

reduction in the risk of progression or death with A+AVD vs ABVD

(HR 0.64; 95% CI, 0.45‐0.92; P =0.013) with a 5‐year PFS of 86.3%

vs 79.4%, respectively, similar to the ITT population. The PFS beneﬁt

of A+AVD vs ABVD was independent of PET2 status; PET2 positivity

(Deauville 4‐5) was 6% and 8%, respectively.

On the A+AVD arm, 81 pts (20%) had at least one subsequent

anticancer therapy (including radiotherapy) vs 96 pts (26%) on the

ABVD arm; 26 pts (7%) on the A+AVD arm received subsequent high

dose chemotherapy and autologous stem cell transplant vs 32 pts

(9%) on the ABVD arm.

Any‐grade peripheral neuropathy (PN) occurred in 64% and 40% of

pts on the A+AVD and ABVD arms, respectively. Resolution or

improvement of PN occurred in 88‐89% of pts on both arms. Ongoing

PN was predominantly Gr 1 (62%) and Gr 2 (26%), with 8 pts (3% of

the total cohort) on the A+AVD arm and 1 pt (<1%) on the ABVD

arm reporting ongoing Gr 3 PN. Seven pts (1.8%) and 5 pts (1.4%) on

the A+AVD and ABVD arms, respectively, reported a secondary

malignancy.

Subsequent pregnancies were reported in female pts (44 A+AVD; 26

ABVD) and partners of male pts (31 A+AVD; 30 ABVD). No stillbirths

were reported. All but 1 pt in each arm was <40.

Conclusions: Consistent with the ITT population, AYAs treated

with A+AVD compared to ABVD had a durable PFS beneﬁt at this

signiﬁcant 5‐year milestone. No impact on the rate of secondary

malignancies and a numerically greater number of pregnancies

were observed, outcomes of interest to AYAs. Additionally,

the majority of PN events improved or resolved over time. A+AVD

should be considered a treatment option for AYAs with stage

III/IV cHL.

EA ‐previously submitted to ASCO and EHA 2021.

The research was funded by: Seagen Inc.

Keywords: Hodgkin lymphoma

Conﬂicts of interests pertinent to the abstract

H. E. Crosswell

Consultant or advisory role: Servier, Daiichi Sankyo

Stock ownership: Kiyatec, BMS, Seagen Inc., Gliead Sciences, Abbvie,

Pﬁzer

SUPPLEMENT ABSTRACTS

A. S. LaCasce

Consultant or advisory role: Forty Seven, BMS, Seagen Inc.,

Humanigen

Research funding: Sanoﬁ, Celgene, Seagen Inc.,

Other remuneration: Speakers' Bureau ‐Research to Practice

N. L. Bartlett

Consultant or advisory role: Seagen Inc., Roche/Genentech, ADC

Therapeutics, BTG, Acerta Pharma

Research funding: Seagen Inc., Kite Pharma, Merck, BMS, Celgene,

Immune Design, Forty Seven, Janssen, Pharmacyclics, Millennium,

ADC Therapeutics, Autolus, Roche/Genentech, Pﬁzer, Afﬁrmed

Therapeutics

D. J. Straus

Consultant or advisory role: Takeda, Seagen Inc.

Research funding: Seagen Inc.

K. J. Savage

Consultant or advisory role: Seagen Inc., BMS, Merck, Servier, Abb-

vie, Gilead Sciences, AstraZeneca

Honoraria: Seagen Inc., BMS, Merck, Abbvie, Gilead Sciences,

AstraZeneca, Kyowa Kirin, Novartis, Novartis Canada Pharmaceuti-

cals Inc.

Research funding: Roche, BMS

Educational grants: Seagen Inc.

P. L. Zinzani

Consultant or advisory role: EUSA Pharma, Takeda, Merck, Roche,

Abbvie

Honoraria: EUSA Pharma, Takeda, Merck, Roche, Abbvie

Other remuneration: Speakers' Bureau ‐EUSA Pharma, Takeda,

Merck, Gilead Sciences, Novartis

G. P. Collins

Consultant or advisory role: Roche, Takeda, Incyte, Pﬁzer, MSD, Celgene,

Beigene, Daiichi Sankyo, Celleron Therapeutics, ADC Therapeutics

Honoraria: Roche, Takeda, Gilead Sciences, Pﬁzer, Novartis, Daiichi

Sankyo, Incyte, Celleron Therapeutics, MSD Oncology, BeiGene, ADC

Therapeutics

Research funding: MSD Oncology, Celgene, Celleron Therapeutics,

BMS, Amgen

Other remuneration: Speakers' Bureau ‐Roche, Takeda, Novartis,

Gilead Sciences

M. A. Fanale

Employment or leadership position: Seagen Inc.

Consultant or advisory role: Spectrum Pharmaceuticals, Amgen,

Merck, BMS, Seagen Inc.

Stock ownership: Seagen Inc.

Honoraria: Seagen Inc., Takeda, Research to Practice, Plexus, BMS

Research funding: Millennium, Seagen Inc., Novartis, MedImmune,

Celgene, Molecular Templates, Genentech, Gilead Sciences, BMS,

Merck, ADC Therapeutics, Pharmacyclics, Takeda

Educational grants: Takeda, Spectrum Pharmaceuticals, Research to

Practice, Plexus, BMS, Merck, Seagen Inc.

K. Fenton

Employment or leadership position: Seagen Inc.

Stock ownership: Seagen Inc.

Educational grants: Seagen Inc.

C. Dong

Employment or leadership position: Takeda

Stock ownership: Seagen Inc., Takeda

H. H. Miao

Employment or leadership position: Takeda

Stock ownership: Takeda

A. P. Grigg

Consultant or advisory role: MSD Oncology, Janssen, Novartis

Honoraria: Roche, MSD

039 |A UK POPULATION‐BASED STUDY OF NON‐HODGKIN

LYMPHOMA IN TEENAGERS AND YOUNG ADULTS (TYA) ‐

INCIDENCE, TREATMENT AND OUTCOMES

R. Carr

, A. Davies

, B. Uttenthal

, M. Lamb

, J. Fidalgo

B. Carpenter

Guy's & St Thomas' Hospital, Haematology, London, UK,

Southampton

NCRI/CR UK Experimental Cancer Medicines Centre, Haematology,

Southampton, UK,

Addenbrookes Hospital, Paediatric Oncology,

Cambridge, UK,

Department of Health Sciences University of York,

Haematological Malignancy Research Network, York, UK,

University

College Hospital, Haematology, London, UK

Introduction: NHL is a common malignancy in young people.

The disease spectrum differs from older adults, it is frequently

difﬁcult to manage and few recruited into trials. To gain a whole

population view of disease incidence and outcomes, and provide

evidence for trial design and optimised treatment strategies, this

study examines diagnosis, treatment and outcome data from 2 co-

horts of patients.

Methods: The 2 study cohorts comprises patients aged 15 to 29y;

i) a 3 year ‘Population Cohort’ of all cases diagnosed in England

2015‐2017 based on Cancer Registry records; ii) a 4 year

contemporaneous ‘Consented Study Cohort’ of patients recruited

at 29 hospitals, 21 being Regional Cancer Centres, diagnosed over

4y 2015‐2018. Population data includes demographics, diagnosis,

place of care, vital status; Consented data includes diagnostic pa-

thology, staging, treatment and response, with relapses and deaths

to January 2021.

Results: Population Cohort 624 patients with 22 NHL sub‐types.

Incidence increased with age, 15‐19y (n =123) 20‐24y (n =206) 25‐

29y (n =295), particularly Diffuse Large B‐cell Lymphoma (DLBCL) (n

SUPPLEMENT ABSTRACTS

=43, 70, 124, by age respectively). All NHL sub‐types were more

common in males except for Mediastinal B‐cell (PMBL) more com-

mon in females. For all NHLs combined, survival was not inﬂuenced

by gender or age but differed by place of care. 2y OS of patients aged

15‐24y treated at the 29 Consented Study hospitals was 86% and

74% at other, mostly smaller district hospitals, Hazard Ratio 1.75

(0.94, 3.26).

Consented Study Cohort 392 patients were recruited, 15‐19y (n =

111), 20‐24y (n =148), 25‐29y (n =133). 27 NHL sub‐types were

recorded. Presentation with advanced disease was common; of 104

DLBCLs, 15% had NCCI IPI score of 4‐5 and 18% had ≥3 extranodal

disease sites.

Unexpected was frequent failure to respond to ﬁrst‐line therapy in

DLBCL and PMBL. 8/81 (10%) DLBCLs with complete treatment

records died with refractory disease and 9 (11%) required ≥2 lines

to achieve remission. 4/60 (7%) PMBLs died with refractory dis-

ease and 19 (32%) remained PET positive after ﬁrst‐line chemo-

therapy, needing further chemotherapy or radiotherapy to achieve

remission.

There was variation between hospitals in treatment regimens

used for individual diseases. The effect of treatment on survival

being most marked for Burkitt's Lymphoma aged 15‐24y. Of a

total 32 cases, 23 were treated with (R)CODOX‐M±IVAC, 7

died (OS 69%); 9 treated on the (R)FAB/LMB96 protocol, 1 died

(OS 89%). This observation needs investigation in a randomised

trial.

Conclusions: NHL in teenage and young adult patients is challenging

to manage. Advanced disease and resistance to ﬁrst line treatment is

common. Our ﬁndings support treatment of these cases guided by

experienced cancer centres. The detailed information gained by this

national collaboration provides the evidence base for future trials

and treatment strategies.

The research was funded by: Leukaemia UK

Gilead UK and Ireland Fellowship Programme

Keywords: Non‐Hodgkin (Pediatric, Adolescent, and Young

Adult)

No conﬂicts of interests pertinent to the abstract.

SESSION 6: LYMPHOMA BIOLOGY 1

040 |MOLECULAR SUBCLUSTERS OF FOLLICULAR

LYMPHOMA: A REPORT FROM THE UK's HAEMATOLOGICAL

MALIGNANCY RESEARCH NETWORK

S. Crouch

, D. Painter

, S. Barrans

, E. Roman

, P. Beer

, S. Lacy

S. Cooke

, N. Webster

, P. Glover

, S. van Hoppe

, P. J. Campbell

D. J. Hodson

, R. Patmore

, C. Burton

, A. G. Smith

, R. Tooze

University of York, Epidemiology and Cancer Statistics Group,

Department of Health Sciences, York, UK,

Leeds Teaching Hospitals

NHS Trust, Haematological Malignancy Diagnostic Service, Leeds, UK,

University of Glasgow, Glasgow Precision Oncology Laboratory,

Glasgow, UK,

Wellcome Trust Sanger Institute, Cancer, Ageing and

Somatic Mutation Programme, Cambridge, UK,

University of

Cambridge, Wellcome–MRC CambridgeStem Cell Institute, Cambridge,

UK,

Hull University Teaching Hospitals NHS Trust, Queen's Centre for

Oncology and Haematology, Hull, UK

Follicular lymphoma (FL), while underpinned by apparently

shared molecular pathogenesis, reﬂects a heterogeneous disease

entity. At a molecular level it remains unclear whether FL can be

resolved into recurrent mutational clusters or pathogenetic

pathways.

Here we report the results of targeted sequencing (293 genes) and

robust cluster analysis as previously applied in DLBCL to a

population‐based cohort of FL (n =548) from the Haematological

Malignancy Research Network (catchment population of ∼4 million,

14 centers). This cohort with full clinical follow‐up includes 96 cases

who underwent transformation to DLBCL, with 26 paired samples

sequenced.

FL cases had a median of 6 (IQR 4‐8) driver mutations per sample.

Most prevalent events were in KMT2D,CREBBP,BCL2,TNFRSF14,

EZH2,STAT6 &BCL7A. The most common mutation hot spots were

EZH2 codon 646, and STAT6 codon 419. Potential targets (22 genes)

of aberrant somatic hypermutation (aSHM) were amongst the most

frequently mutated. After signal‐to‐noise ﬁltering 31 genetic features

were suitable for cluster analysis. The stringent Bayesian Information

Criterion (BIC) or sensitive Akaike Information Criterion (AIC)

resolved 2 (BIC) or 3 (AIC) robust clusters. Both separated FL with

multiple aSHM target gene mutations (FL_aSHM) from the

remainder. AIC resolved FL_aSHM (10.6%), and FL characterized by

STAT6,CREBBP and TNFRSF14 mutations (21.0%, FL_STAT6) from

the remainder (FL_Com, 68.4%). No signiﬁcant differences in sex or

FLIPI were evident between the clusters. Patients in FL_aSHM were,

on average, 4.8 years older than those in other clusters (p =0.007).

Stage distributions differed: FL_aSHM had excess of stage III,

FL_STAT6 of stages I & II, and FL_Com of stage IV. No overall survival

(OS) differences between clusters were detected in patients initially

managed by Watch and Wait, but OS AIC cluster differences were

detectable in those initially managed in other ways (p =0.04). Evi-

dence for an adverse OS outcome for FL_aSHM relative to FL_Com (p

=0.03), did not persist after adjustment for age. The strongest pre-

dictor for OS at individual gene level was aSHM target HIST1H2AC

(HR =3.10, 95% CI =1.64, 5.86). Transformation showed no evi-

dence of imbalance between FL molecular subtypes, while 2‐genes

(TP53 and CDKN2A) were linked in univariate modelling to adverse

hazard ratios. The predominant mutational pattern in 26‐paired

transformation subjects supported branching evolution.

This population‐based analysis provides evidence for distinct mech-

anistic entities in FL, with aSHM burden and STAT6 mutation status

providing key determinants of this heterogeneity. In contrast to

DLBCL, we did not ﬁnd evidence that tumour genetics provides a

strong marker for predicting patient outcome in FL. Instead we

speculate that factors related to the microenvironment or host im-

mune system may have a greater inﬂuence on patient survival.

SUPPLEMENT ABSTRACTS

The research was funded by: Blood Cancer UK (grant num-

ber 15037), Cancer Research UK (grant number A29685) and the

National Institute for Health Research (grant number RP‐PG‐0613‐

20002) funded the majority of this study. Genetic sequencing

was funded by 14M Genomics, a start‐up company that ceased

trading February 2016. DJH was funded by a clinician scientist

fellowship from the MRC and receives core funding from Well-

come and MRC to the Wellcome‐MRC Cambridge Stem Cell

Institute.

Keywords: Genomics, Epigenomics, and Other ‐Omics, Indolent

non‐Hodgkin lymphoma, Pathology and Classiﬁcation of

Lymphomas

No conﬂicts of interests pertinent to the abstract.

041 |SOMATIC ALTERATIONS IN FOLLICULAR LYMPHOMA

ASSOCIATE WITH UNIQUE TUMOR‐CELL TRANCRIPTIONAL

STATES AND TUMOR‐IMMUNE MICROENVIRONMENTS

J. Krull

, K. Wenzl

, M. K. Manske

, M. A. Hopper

, M. C. Larson

V. Sarangi

, P. Barman

, M. R. Serres

, S. Khan

, A. J. Novak

M. J. Maurer

, Z. Yang

, L. Rimsza

, B. K. Link

, T. M. Habermann

S. M. Ansell

, R. L. King

, J. R. Cerhan

, J. P. Novak

Mayo Clinic, Hematology, Rochester, Minnesota, USA,

Mayo Clinic,

Health Science Research, Rochester, Minnesota, USA,

Mayo Clinic,

Laboratory Medicine and Pathology, Phoenix, Arizona, USA,

University of

Iowa, Hematology, Iowa City, Iowa, USA,

Mayo Clinic, Hematopathology,

Rochester, Minnesota, USA

Background: While signiﬁcant advances have been made in our un-

derstanding of FL biology, genomic studies to date have primarily

focused on prognostic (M7‐FLIPI), pathological designation (Grade 1‐

3b), or understanding transformation to DLBCL. Conclusions from

these studies are based on either small cohorts or targeted

sequencing panels, with no larger‐scale, integrated WES and RNAseq

studies being performed. Together, this presents an opportunity for a

comprehensive characterization of FL. Using a novel cohort of 93 FL

tumors, we have explored the transcriptomic signature of puriﬁed FL

B cells, and identiﬁed unique molecular subsets which are deﬁned by

distinct pathway activation, immune content, and genomic

signatures.

Methods: Frozen pre‐treatment tumor biopsies from 93 FL patients

enrolled in the University of Iowa/Mayo Clinic Lymphoma SPORE

were used. RNAseq on MACS sorted FL B cells and WES was per-

formed and processed in the Mayo Clinic Genome Analysis Core.

Novel driver genes were identiﬁed using 20/20+driver analysis.

Matching CyTOF data was aquired from a previously published

SUPPLEMENT ABSTRACTS

dataset. Downstream analyses were perfomed in R using established

packages.

Results: Unsupervised clustering of RNAseq data identiﬁed three

distinct patient groups, C1 (n =24) and C2 (n =25), and C3 (n =

43). NMF‐derived cluster metagenes revealed signiﬁcant pathway

association with DNA repair and stress response (C1), type‐I IFN

signaling (C2), and epigenetic modulation (C3), differentiating be-

tween the 3 groups. VIPER master regulator activity inferencing

revealed that these pathways were likely being controlled by dif-

ferential activity in NF‐kB, IRFs, STAT1, BCL6, and FOXO1. The

metagenes signiﬁcantly enriched for remnants of speciﬁc germinal

center programs, such as light‐zone (C1), pre‐memory (C2), and a

pre‐light‐zone intermediate (C3). To assess the contribution of the

tumor microenvironment (TME), available paired CyTOF data

revealed a wide variety of immune content in C1 that consisted

mostly of Tfh and myeloid cells, an active TME in C2, with sig-

niﬁcant quantities of CD8 T cell and NK cell populations, and a

poorly populated immune compartment in C3, compared to C1 and

C2. Finally, somatic driver mutations and copy number alterations

from WES were identiﬁed, and associated with the three clusters.

The three groups distinguished themselves by signiﬁcant enrich-

ment of alterations in TNFAIP3 (C1), host defense genes SNRNP200

and IRF8 (C2) and chromatin modiﬁers such as KMT2D and

CREBBP (C3).

Conclusion: Using a multi‐omic approach, three unique FL tumor B

cell states were identiﬁed which are linked to speciﬁc genetic

events and TME composition. This study improves the under-

standing of the mechanisms driving FL tumors and motivates

further investigation into transcriptional consequences of genetic

events, as well as potential tumor intrinsic factors that may in-

ﬂuence the TME.

The research was funded by: NIH‐P50 CA097274 to J.R.C. and

A.J.N.

Keywords: Genomics, Epigenomics, and Other ‐Omics, Tumor Biology

and Heterogeneity, Indolent non‐Hodgkin lymphoma

Conﬂicts of interests pertinent to the abstract

J. Krull

Research funding: Bristol Myers Squibb

J. P. Novak

Research funding: Bristol Meyers Squibb

042 |CREBBP MEDIATED ACETYLATION OF KMT2D IN

NORMAL AND TRANSFORMED GC B CELLS

S. Vlasevska

, L. Garcia‐Ibanez

, R. Duval

, A. B. Holmes

, R. Jahan

K. Basso

, R. Dalla‐Favera

, L. Pasqualucci

Columbia University, Institute for Cancer Genetics, New York, New

York, USA,

Columbia University, Institute for Cancer Genetics, the

Department of Pathology and Cell Biology, and the Herbert

Irving Comprehensive Cancer Center, New York, New York,

USA

Introduction: Perturbation of epigenetic reprogramming is a hall-

mark of germinal center (GC) derived follicular lymphoma (FL) and

diffuse large B cell lymphoma (DLBCL), which harbor highly recurrent

somatic mutations of histone/chromatin modiﬁer genes. Among these

genes, those encoding the KMT2D methyltransferase and the

CREBBP acetyltransferase are the most commonly mutated,

respectively accounting for 60‐80% of FL and >40% of DLBCL

belonging to the EZB/C3 genetic subgroup. We have shown that

these enzymes represent early events in the history of FL/DLBCL,

and act as haploinsufﬁcient tumor suppressors by accelerating the

development of BCL2‐translocation driven lymphomas in vivo. The

aim of this study was to investigate the functional interaction be-

tween KMT2D and CREBBP and their combined role in vivo in

lymphomagenesis.

Methods: We used biochemical and genetic approaches to investi-

gate whether KMT2D is a substrate of CREBBP‐mediated acetyla-

tion, contrast their chromatin binding pattern (ChIP‐Seq), and study

the functional relevance of this post‐translational modiﬁcation in

normal GC B cells and DLBCL. Compound GC‐speciﬁc Crebbp;Kmt2d

haplo‐insufﬁcient mice, mimicking the frequent co‐existence of these

lesions in FL and DLBCL, were then interrogated to assess the bio-

logical consequences of this interaction in GC responses and

lymphomagenesis.

Results: We found that KMT2D is acetylated in GC B cells as well

as in DLBCL cell lines carrying wildtype (WT) CREBBP/KMT2D

alleles. CREBBP catalyzes this modiﬁcation in vitro and in vivo, and

this activity is lost in lymphoma‐associated CREBBP proteins car-

rying truncating or missense mutations inactivating the HAT

domain. Loss‐of function assays in isogenic WT vs CREBBP‐or

EP300 deﬁcient DLBCL cells showed that CREBBP is the prefer-

ential acetyltransferase. Of note, genetic disruption or pharmaco-

logic blockade of CREBBP led to a measurable reduction in

H3K4me1, the histone modiﬁcation catalyzed by KMT2D, indi-

cating a role for KMT2D acetylation in modulating its enzymatic

activity. In vivo, GC‐speciﬁc combined haploinsufﬁciency of

KMT2D and CREBBP induced GC hyperplasia which was signiﬁ-

cantly more prominent as compared to individual deletion of these

two genes.

Conclusions: Our data reveal a physiologically relevant role for

CREBBP in acetylating the KMT2D protein, and suggest that

this post‐translational modiﬁcation acts as a modulator of its activity.

These ﬁndings imply that CREBBP mutant tumors bear

KMT2D functional insufﬁciency, suggesting that CREBBP/KMT2D

haploinsufﬁciency facilitates the expansion of the common precursor

cell before acquisition of secondary genetic events leading to FL and/

or DLBCL. CREBBP‐targeted epigenetic therapies may add to the

therapy in KMT2D mutated tumors.

SUPPLEMENT ABSTRACTS

Keywords: Genomics, Epigenomics, and Other ‐Omics,

Aggressive B‐cell non‐Hodgkin lymphoma, Indolent non‐Hodgkin

lymphoma

No conﬂicts of interests pertinent to the abstract.

043 |GENETIC AND PHENOTYPIC ATTRIBUTES OF SPLENIC

MARGINAL ZONE LYMPHOMA

F. Bonﬁglio

, A. Bruscaggin

, F. Guidetti

, L. Terzi di Bergamo

M. Faderl

, V. Spina

, A. Condoluci

, L. Bonomini

, G. Forestieri

R. Koch

, D. Piffaretti

, K. Pini

, M. C. Pirosa

, M. G. Cittone

A. Arribas

, M. Lucioni

, G. Ghilardi

, W. Wu

, L. Arcaini

M. J. Baptista

, G. Bastidas

, S. Bea

, R. Boldorini

, A. Broccoli

V. Canzonieri

, L. Cascione

, L. Ceriani

, S. Cogliatti

E. Derenzini

, L. Devizzi

, S. Dietrich

, A. R. Elia

, F. Facchetti

G. Gaidano

, J. F. Garcia

, B. Gerber

, P. Ghia

, M. G. Da Silva

G. Gritti

, A. Guidetti

, F. Hitz

, G. Inghirami

, M. Ladetto

A. Lopez‐Guillermo

, E. Lucchini

, A. Maiorana

, R. Marasca

E. Matutes

, V. Meignin

, M. Merli

, A. Moccia

, M. Mollejo

C. Montalban

, U. Novak

, D. G. Oscier

, F. Passamonti

F. Piazza

, S. Pizzolitto

, E. Sabattini

, G. Salles

, E. Santam-

brogio

, L. Scarfó

, A. Stathis

, G. Stüssi

, J. T. Geyer

, G. Tapia

C. Thieblemont

, T. Tousseyn

, A. Tucci

, C. Visco

, U. Vitolo

T. Zenz

, P. L. Zinzani

, H. Khiabanian

, A. Calcinotto

F. Bertoni

, G. Bhagat

, E. Campo

, L. De Leval

, S. Dirnhofer

S. A. Pileri

, M. Án. Piris

, A. Traverse‐Glehen

, A. Tzankov

M. Paulli

, M. Ponzoni

, L. Mazzucchelli

, F. Cavalli

, E. Zucca

D. Rossi

Institute of Oncology Research, Experimental Hematology, Bellinzona,

Switzerland,

Oncology Institute of Southern Switzerland, Division of

Hematology, Bellinzona, Switzerland,

International Extranodal

Lymphoma Study Group, IELSG, Bellinzona, Switzerland,

Institute of

Oncology Research, Lymphoma Genomics, Bellinzona, Switzerland,

Fondazione IRCCS Policlinico San Matteo, Unit of Anatomic

Pathology, Pavia, Italy,

Fondazione IRCCS Policlinico San Matteo,

Division of Hematology, Pavia, Italy,

Josep Carreras Leukaemia

Research Institute, Lymphoid neoplasms Group, Badalona, Spain,

Hospital Clínic i Provincial de Barcelona, Division of Hematology,

Barcelona, Spain,

Hospital Clínic, Pathology Department, Barcelona,

Spain,

University of Eastern Piedmont, Division of Pathology, Novara,

Italy,

IRCCS Azienda Ospedaliero‐Universitaria di Bologna, Istituto di

Ematologia, Bologna, Italy,

CRO Aviano National Cancer Institute,

Pathology Unit, Aviano, Italy,

Imaging Institute of Southern

Switzerland, Clinic of Nuclear Medicine and PET‐CT centre, Bellinzona,

Switzerland,

Kantonsspital St. Gallen, St.Gallen, Institute of Pathol-

ogy, St.Gallen, Switzerland,

IEO, European Institute of Oncology

IRCCS, Onco‐hematology Div., Milan, Italy,

Fondazione IRCCS Isti-

tuto Nazionale dei Tumori di Milano, Division of Hematology, Milan,

Italy,

University Hospital Heidelberg, Division of Hematology, Hei-

delberg, Germany,

Institute of Oncology Research, Cancer

Immunotherapy, Bellinzona, Switzerland,

University of Brescia School

of Medicine, Department of Molecular and Translational Medicine,

Brescia, Italy,

University of Eastern Piedmont, Division of hematol-

ogy, Novara, Italy,

MD Anderson Cancer Center, Division of Pa-

thology, Madrid, Spain,

IRCCS Ospedale San Raffaele and Università

Vita‐Salute San Raffaele, Division of Hematology, Milan, Italy,

Instituto Português de Oncologia de Lisboa, Division of Hematology,

Lisbon, Portugal,

Azienda Ospedaliera Papa Giovanni XXIII, Division

of Hematology, Bergamo, Italy,

Kantonsspital St. Gallen, Division of

Hematology, St. Gallen, Switzerland,

Weill Cornell Medical College,

Department of Pathology and Laboratory Medicine, New York, New

York, USA,

Azienda Ospedaliera SS Antonio e Biagio, Division of

Hematology, Alessandria, Italy,

Hospital Clínic i Provincial de Bar-

celona, Division of Lymphoid neoplasms, Barcelona, Spain,

Azienda

Sanitaria Universitaria Giuliano Isontina, Division of Hematology,

Trieste, Italy,

Universitá degli Studi di Modena e Reggio Emilia, Di-

vision of Pathology, Modena, Italy,

University of Modena and Reggio

Emilia, Department of Medical and Surgical Sciences, Modena, Italy,

Hospital Clínic i Provincial de Barcelona, Haematopathology Unit,

Barcelona, Spain,

Saint Louis Hospital, Division of Pathology, Paris,

France,

University of Insubria and ASST Sette Laghi, Ospedale di

Circolo of Varese, Division of Hematology, Varese, Italy,

Oncology

Institute of Southern Switzerland, Clinic of Medical Oncology, Bellin-

zona, Switzerland,

Hospital Virgen de la Salud, Division of Pathology,

Toledo, Spain,

MD Anderson Cancer Center, Division of Hematology,

Madrid, Spain,

University Cancer Center, Inselspital, Department of

Medical Oncology, Bern, Switzerland,

Royal Bournemouth Hospital,

Division of Hematology, Bournemouth, UK,

University of Insubria

and ASST Sette Laghi, Ospedale di Circolo of Varese, Department of

Medicine and Surgery, Varese, Italy,

Ospedale Universitario di

Padova, Division of Hematology, Padova, Italy,

Policlinico Uni-

versitario, Division of Pathology, Udine, Italy,

S. Orsola‐Malpighi

Hospital, University of Bologna, Department of Experimental Diag-

nostic and Specialty Medicine, Bologna, Italy,

Université de Lyon,

Faculté de Médecine et de Maïeutique Lyon Sud, Lyon, France,

Candiolo Cancer Institute, FPO‐IRCCS, Division of Hematology,

Candiolo, Italy,

Weill Cornell Medical College, Division of Anatomic

Pathology and Clinical Pathology, New York, USA,

Hospital Germans

Trias I Pujol, Division of Pathology, Barcelona, Spain,

APHP, Hopital

Saint‐Louis, Hemato‐oncology unit, Paris, France,

University Hospitals

Leuven, Department of Haematology, Leuven, Belgium,

Spedali Civili,

Division of Hematology, Brescia, Italy,

University of Verona,

Department of Medicine, Verona, Italy,

University Hospital Zurich,

Department of Medical Oncology and Hematology, Zurich, Switzerland,

Università di Bologna, Dipartimento di Medicina Specialistica, Diag-

nostica e Sperimentale, Bologna, Italy,

Rutgers University, Center for

Systems and Computational Biology, New Brunswick, USA,

Columbia

University, Department of Pathology and Cell Biology, New York, USA,

Institut universitaire de pathologie, Division of Pathology, Lausanne,

Switzerland,

University Hospital Basel, Institute of Pathology and

Medical Genetics, Basel, Switzerland,

European Institute of Oncology

SUPPLEMENT ABSTRACTS

IRCCS, Haematopathology Division, Milan, Italy,

Fundación Jiménez

Díaz, Pathology Service, Madrid, Spain,

Centre Hospitalier Lyon Sud,

Division of Pathology, Lyon, France,

San Raffaele Scientiﬁc Institute,

Ateneo Vita‐Salute San Raffaele University and Pathology Unit, Milan,

Italy,

Cantonal Institute of Pathology, Pathology unit, Locarno,

Switzerland,

Institute of Oncology Research, Bellinzona, Switzerland

FB, AB, FG equally contributed

*EZ, DR equally contributed

Introduction: Splenic marginal zone B‐cell lymphoma (SMZL) is a

heterogeneous entity. The clinical course is variable, mutated genes

are multiple with no unifying mechanism, essential regulatory path-

ways and surrounding microenvironments are diverse. We sought to

provide a unifying view of SMZL by resolving its heterogeneity in

subgroups sharing genomic abnormalities, pathway signatures and

microenvironment compositions to uncover biomarkers and thera-

peutic vulnerabilities.

Methods: We studied 303 pathologically conﬁrmed SMZL spleen

samples collected through the IELSG46 multicenter, international

study (NCT02945319). The study cohort was representative of SMZL

in terms of demographics, clinical features and outcome. We carried

out a genetic and phenotypic analysis, deﬁned self‐organized signa-

tures, validated them in independent primary tumors meta‐data and

in genetically modiﬁed mouse models, and correlated them with

outcome data.

Results: We identiﬁed and validated two prominent and self‐

aggregating genetic clusters in SMZL, termed NNK (58% of

cases, from NF‐kB, NOTCH and KLF2 modules) and DMT (32% of

cases, from DNA‐damage response, MAPK and TLR modules).

NNK‐SMZLs were dominated by mutations of NF‐κB (e.g.,

TNFAIP3, TRAF3, BIRC3), NOTCH (e.g., NOTCH2, NOTCH1,

SPEN) and KLF2. DMT‐SMZLs were characterized by mutations in

DNA damage response pathway genes (e.g., TP53, ATM). Muta-

tions in MAPK (e.g., BRAF) and TLR genes (e.g., MYD88, all

involving positions other than p.L265) were also enriched in DMT‐

SMZLs (Figure A and B). These genetic clusters have distinct un-

derpinning biology. NNK‐SMZLs were enriched of IGHV1‐2*04

allele usage and of 7q deletion, while conversely DMT‐SMZLs were

SUPPLEMENT ABSTRACTS

depleted of both of them (Figure C). NNK‐SMZL expressed

signiﬁcantly higher levels of genes belonging to NOTCH2 pathway

and of genes that are activated by non‐canonical NF‐κB tran-

scription factors. Conversely, DMT‐SMZL had a signature of TP53

and apoptosis impairment (Figure D). Digital cytometry and in situ

proﬁling segregated two basic types of SMZL immune microenvi-

ronment termed inﬂamed SMZL (50% of cases, associated with

inﬂammatory cells and immune checkpoint activation) and non‐

inﬂamed SMZL (50% of cases) (Figure E and F). The combination

of molecular and phenotypic proﬁling allowed to sort out a high

risk clinical subset of patients whose tumor was characterized by

having both NNK genotype and ‘’inﬂamed’’ microenvironment

(Figure G).

Conclusions: Our study highlights the complexity of SMZL. The

molecular framework provides an evolving understanding of

the pathogenesis of SMZL, and can be regarded as a building

block for further reﬁning the classiﬁcation of B‐cell tumors of the

spleen, and for aiding the development of rationally targeted

treatments.

The research was funded by: Swiss Cancer League, ID 3746, 4395

4660, and 4705, Bern, Switzerland; Research Advisory Board of the

Ente Ospedaliero Cantonale, ABREOC 2019‐22514, Bellinzona,

Switzerland; European Research Council (ERC) Consolidator Grant

CLLCLONE, ID: 772051; Swiss National Science Foundation, ID

320030_169670/1, 310030_192439, 320036_179318, Berne,

Switzerland; Fondazione Ticinese Contro il Cancro; Fondazione

Fidinam, Lugano, Switzerland; Nelia & Amadeo Barletta Foundation,

Lausanne, Switzerland; Fond’Action, Lausanne, Switzerland; The

Leukemia & Lymphoma Society, Translational Research Program, ID

6594‐20, New York; AFRI, Ente Ospedaliero Cantonale, Bellinzona,

Switzerland; Fondazione Dr. Ettore Balli.

Keywords: Diagnostic and Prognostic Biomarkers, Indolent

non‐Hodgkin lymphoma, Pathology and Classiﬁcation of Lymphomas

Conﬂicts of interests pertinent to the abstract

P. Ghia

Honoraria: AbbVie, ArQule/MSD, AstraZeneca, Beigene, Celgene/

Juno(BMS, Gilead, Janssen, Loxo/Lilly, Roche

Research funding: AbbVie, AstraZeneca, Gilead, Janssen, Sunesis

G. Gritti

Consultant or advisory role: Takeda, IQvia, Gilead Sciences

Research funding: Gilead Sciences

Educational grants: Roche, Abbvie, Gilead Sciences, Abbvie

A. Moccia

Consultant or advisory role: Roche, Janssen and Takeda

L. Scarfó

Honoraria: AbbVie, AstraZeneca and Janssen

D. Rossi

Honoraria: AbbVie, AstraZeneca, Janssen

Research funding: AbbVie, AstraZeneca, Janssen

044 |MONOMORPHIC EPITHELIOTROPIC INTESTINAL T‐CELL

LYMPHOMA (MEITL): CLINICO‐PATHOLOGICAL ANALYSIS OF A

MULTICENTER EUROPEAN COHORT

D. Cavalieri

, O. Tournilhac

, E. Missiglia

, C. Bonnet

, A. Ledoux‐

Pilon

, B. Bisig

, A. Cairoli

, E. Poullot

, V. Fataccioli

, M. Parrens

M. C. Copin

, F. Llamas Gutierrez

, L. Xerri

, C. Bossard

, R. De

Wind

, F. Drieux

, F. Lhomme

, A. Daniel

, L. Clément‐Filliatre

F. Lemmonier

, P. Morel

, R. Noël

, T. Brotelle

, S. Glaisner

D. Sibon

, A. El Yamani

, S. Bologna

, K. Queru

, G. Damaj

V. Letailleur

, B. Villemagne

, E. Fleck

, E. Dupont

, E. Tcherno-

nog

, H. Monjanel

, V. de Wilde

, D. Vallois

, P. Gaulard

L. de Leval

CHU de Clermont‐Ferrand, Service d'Hematologie Clinique et de

Therapie Cellulaire, Clermont‐Ferrand, France,

Lausanne University

Hospital, Lausanne University, Institute of pathology, Lausanne,

Switzerland,

CHU Sart Tilman, Department of Hematology, Liège,

Belgium,

CHU de Clermont‐Ferrand, Service d'anatomie pathologique,

Clermont‐Ferrand, France,

Lausanne University hospital, Lausanne

University, Service of Hematology, Department of Oncology, Lausanne,

Switzerland,

Hôpitaux Universitaires Henri Mondor, AP‐HP, Departe-

ment de Pathologie, France,

Université Paris Est Créteil, INSERM,

Institut Médical de Recherche Biomédicale, Créteil, France,

CHU de

Bordeaux, Service d'anatomie pathologique, Bordeaux, France,

CHU de

Lille, Service d'anatomie pathologique, Lille, France,

CHU de Rennes,

Service d'anatomie pathologique, Rennes, France,

Institut Paoli

Calmettes, Service d'anatomie pathologique, Marseille, France,

CHU

de Nantes, Service d'anatomie pathologique, Nantes, France,

Institut

Jules Bordet, Université libre de Bruxelles, Department of pathology,

Bruxelles, Belgium,

Centre Henri Becquerel, Service d'anatomie

pathologique, Rouen, France,

CHU de Rennes, Service d'hématologie

clinique, Rennes, France,

CHU de Lille, Service d'hématologie clinique,

Lille, France,

CHRU Nancy, Service d'hématologie clinique, Nancy,

France,

Hôpitaux Universitaires Henri Mondor, APHP, Université Paris

Est‐Créteil, Unité Hémopathies Lymphoïdes, INSERMU955, Créteil,

France,

CHU d'Amiens, Service d'hématologie clinique, Amiens,

France,

Institut Paoli Calmettes, Service d'hématologie clinique,

Marseille, France,

CH d'Avignon, Service d'hématologie clinique,

Avignon, France,

Institut Curie‐Hôpital René Huguenin, Service

d'hématologie clinique, Saint‐Cloud, France,

Necker University Hos-

pital, AP‐HP, Paris Descartes University ‐Sorbonne Paris Cité, Hema-

tology department, Paris, France,

CH de Blois, Service d'hématologie

clinique, Blois, France,

Clinique Louis Pasteur, Service d'oncologie,

Essey‐Lès‐Nancy, France,

CHU de Limoges, Service d'hématologie

clinique, Limoges, France,

Institut d'Hématologie de Basse‐Normandie,

Service d'hématologie clinique, Caen, France,

CHU de Nantes, Service

d'hématologie clinique, Nantes, France,

CHD Vendée, Service d'hém-

atologie clinique, La‐Roche‐Sur‐Yon, France,

GH Littoral Atlantique,

Service d'oncologie, La Rochelle, France,

CH Agen‐Nerac, Service de

médecine interne, Agen, France,

CHU de Montpellier, Service d'hém-

atologie clinique, Montpellier, France,

CH d'Aurillac, Service d'héma-

tologie clinique, Aurillac, France,

Hôpital Erasme, Hematology

SUPPLEMENT ABSTRACTS

department, Bruxelles, Belgium,

Hôpitaux universitaires Henri Mon-

dor, AP‐HP, Université Paris Est‐Créteil, Département de pathologie,

INSERMU955, Créteil, France

Introduction: Monomorphic epitheliotropic intestinal T‐cell lym-

phoma (MEITL) is a rare aggressive primary intestinal T‐cell lym-

phoma. Most case series were reported in Asia. Here we present a

detailed clinico‐pathological analysis of a European cohort.

Methods: Fourty‐nine patients (pts) diagnosed with MEITL between

2005 and 2020 were retrived from 42 LYSA centers in France,

Belgium and Switzerland. Pathology was reviewed and conﬁrmed in

all cases, complete immunophenotypic proﬁles were generated, and

mutation status of 27 relevant genes was obtained by targeted or

whole exome sequencing in 44 cases. Clinical, imaging, and survival

data were collected.

Results: Median age was 69y (29‐91), 55% were men.

Among 34 pts with anamnestic information: one carried a diagnosis

of coeliac disease, screening for coeliac disease was negative in 12/12

pts tested. 30 pts (88%), presented with abdominal emergency

(bowel perforation n =23 and/or obstruction n =11). B symptoms,

cytopenia and inﬂammation were found in 65% (n =22), 41% (n =14)

and 94% (n =32). FDG‐PET/CT showed hypermetabolic lesions with

a high SUVmax (8 to 30).

On the whole cohort of 49 pts : intestinal involvement distribution

was small bowel (n =47), large bowel (n =7), anal (n =1) and

stomach (n =1). Multifocal intestinal involvement was seen in 9 pts.

The Ann Arbor stage was I E (n =15), II E (n =11), and IV (n =15),

missing data (MD) (n =8).

In the 49 pts, the phenotype was CD2+(51%) CD3+(98%) CD4‐

(94%) CD5‐(96%) CD7+(98%) CD8+(88%) CD56+(90%) CD103+

(91%) CD79a‐(90%) EBER‐(98%) with activated cytotoxic proﬁle.

CD30 and aberrant CD20 expression were detected in 0% and 23%.

TCR was γδ (n =20), αβ(n =5), double positive (n =5) or double

negative (n =11).

SETD2 was mutated (n =38), deleted (n =9) or both (n =6) and 38/

42 showed defective H3K36 trimethylation. Other frequent muta-

tions included STAT5B (n =27), JAK3 (n =22), TP53 (n =14).

A 1

line chemotherapy (CT) was recorded in 28 pts including 24

CHOP‐like and 4 autologous transplant, 15 did not receive any CT

(MD =9). Following 1

line, 9 pts reached a CR, and 13 had primary

progression or insufﬁcient response (MD =6). All salvaged pts

eventually died from progression or toxicity.

Among 48 pts with available follow‐up, median OS was 6m (0‐66). In

the 28 pts receiving CT, median OS was 11m (3‐66) and 3‐y OS was

13%. Single or double hit mutations for TP53 and STAT5B were

associated with a worse outcome compared to wild‐type pts (p =

0,004).

Conclusion: In this large European cohort of MEITL, we expand the

extremely poor prognosis related both to the complexity of clinical

presentation and to primary resistance to CHOP‐like poly-

chemotherapy, with a negative impact of single and double‐hit mu-

tations of TP53 and STAT5B. Dynamic management including post‐

operative supportive care, chemotherapy attempt and potential

consolidation by auto‐or even allograft is crucial.

Keywords: Aggressive T‐cell non‐Hodgkin lymphoma

No conﬂicts of interests pertinent to the abstract.

045 |RHOA G17V POTENTIATES CD28 T195P MUTATION

INDUCED NFAT TRANSCRIPTIONAL ACTIVITY UPON CD3/CD28

STIMULATION

D. Vallois

, E. Missiaglia

, B. Bisig

, Mél. Favre Juilland

, M. Thome

Miazza

, L. de Leval

Lausanne University Hospital and Lausanne University, Institute of

Pathology, Lausanne, Switzerland,

Lausanne University, Department of

Biochemistry, Epalinges, Switzerland

Introduction: Recurrent mutations in epigenetic modiﬁers, RHOA and

other genes related to T‐cell receptor (TCR) signaling are found in a

large proportion of angioimmunoblastic T‐cell lymphoma and other

lymphomas derived from follicular T‐helper cells. After RHOA G17V

mutation found in 60‐70% of AITL, CD28 is the most commonly

mutated TCR‐related gene (15%). Since CD28 point mutations co‐

occur with RHOA G17V alteration, we intend to elucidate the po-

tential cooperation of RHOA G17V and CD28 mutations in sustaining

T‐cell proliferation.

SUPPLEMENT ABSTRACTS

Methods: Five stable Jurkat cell lines bearing the two empty vectors

or expressing either RHOA WT or G17V mutant and CD28 WT or

T195P mutant were generated by lentiviral infection and positive

FACS sorting for GFP (RHOA selection) and CD28 expression at the

plasma membrane. We sought for RHOA G17V partners performing

co‐immunoprecipitation experiments with Jurkat cells expressing

empty vector or different RHOA variants (WT, G17V and K18N)

followed by mass spectrometry.

Results: The presence of RHOA G17V and CD28 T195P mutants

induced signiﬁcantly higher levels of IL‐2 secretion and IL‐2tran-

scription than either mutant alone upon CD3/CD28 stimulation,

suggesting a synergistic effect. First, we sought for changes in

phosphorylation of key TCR cytoplasmic transductors upon CD3/

CD28 stimulation. Similar phosphorylation levels were found in

cells harboring both mutants versus CD28 mutant alone. Then we

addressed the activity of NF‐kB, NFAT and AP1 transcription

factors. Luciferase assays showed a signiﬁcant increase of the

transcriptional activity of NFAT and, to a lesser extent, AP1 fac-

tors, in cells harboring both mutants versus either mutant alone.

Thus, in this model the cooperation of RHOA and CD28 mutants

on increased IL2 secretion does not involve increased phosphory-

lation of TCR signaling molecules, but an increased NFAT and AP1

transcription activity. We then searched for RHOA G17V partners

that could explain our observations. Co‐immunoprecipitation anal-

ysis identiﬁed about 20 interactors speciﬁcally associating to

RHOA G17V, among which those most abundant were VAV1 and

the acetyl transferase P300. NFAT luciferase experiments were

conducted with either VAV1 siRNA or P300‐dependent NFAT

transactivation inhibition by expressing the E1A viral protein.

Both VAV1 siRNA and P300 inhibition induced a decreased

NFAT transactivation in cells expressing either mutants alone or

both. Moreover, P300 inhibition by the small molecule A‐485

abolished the increased IL‐2 secretion induced by CD3/CD28

stimulation in cells transfected with RHOA G17V, CD28 T195P, or

both.

Conclusion: Our results suggest that RHOA G17V expression does

not involve increased phosphorylation of TCR signaling molecules but

rather potentiates CD28 T195P‐increased NFAT transactivation

through VAV1 and P300 activities modulation, leading to a syner-

gistic IL2 secretion.

The research was funded by: FNS Grant 310030_172954

Keywords: Tumor Biology and Heterogeneity, Aggressive T‐cell non‐

Hodgkin lymphoma

No conﬂicts of interests pertinent to the abstract.

SESSION 7: AGGRESSIVE EXTRANODAL ENTITIES

046 |NONINVASIVE DETECTION, CLASSIFICATION, AND RISK

STRATIFICATION OF PRIMARY CNS LYMPHOMAS BY CTDNA

PROFILING

J. A. Mutter

, S. Alig

, E. M. Lauer

, M. S. Esfahani

, J. Mitschke

D. M. Kurtz

, M. Olsen

, C. L. Liu

, M. C. Jin

, S. Bleul

C. W. Macaulay

, N. N. Neidert

, D. H. Heiland

, J. Finke

, J. Duyster

J. Wehrle

, M. Prinz

, G. Illerhaus

, P. C. Reinacher

, E. Schorb

M. Diehn

, A. A. Alizadeh

, F. Scherer

SUPPLEMENT ABSTRACTS

University Medical Center Freiburg, Department of Hematology,

Oncology, and Stem Cell Transplantation, Freiburg, Germany,

Stanford

University, Division of Oncology, Department of Medicine, Stanford,

California, USA,

University Medical Center Freiburg, Department of

Neurosurgery, Freiburg, Germany,

University Medical Center Freiburg,

Institute of Neuropathology, Freiburg, Germany,

Klinikum Stuttgart,

Department of Hematology/Oncology and Palliative Care, Stuttgart,

Germany,

University Medical Center Freiburg, Department of

Stereotactic and Functional Neurosurgery, Freiburg, Germany,

Stanford

University, Department of Radiation Oncology, Stanford, California,

USA

Introduction: Circulating tumor DNA (ctDNA) has great potential as

a noninvasive biomarker in diverse systemic lymphomas (Huet et al, J

Clin Oncol 2020). Noninvasive access to tumor‐derived DNA is

particularly appealing for patients with primary CNS lymphoma

(PCNSL), since tumor material otherwise requires invasive surgical

procedures. Here, we explored the value of ctDNA in PCNSL patients

for disease classiﬁcation, MRD detection, and early prediction of

relapse.

Methods: We applied Cancer Personalized Proﬁling by Deep

Sequencing (CAPP‐Seq) to 65 tumor biopsies, 101 blood plasma

specimens, and 43 cerebrospinal ﬂuid (CSF) samples from 68 subjects

with PCNSL, targeting 580 distinct genomic regions. We separately

used Phased variant Enrichment Sequencing (PhasED‐Seq, Kurtz

et al, Nat Biotech 2021; in press) for ultrasensitive ctDNA monitoring.

Levels of ctDNA were correlated with radiological measures of tumor

burden and tested for associations with clinical outcomes. Finally, we

developed a novel machine learning classiﬁer to noninvasively

distinguish CNS lymphomas from other CNS tumors based on their

mutation patterns in plasma and CSF, using supervised training of a

random forest followed by its independent validation.

Results: We identiﬁed genetic aberrations in 100% of PCNSL tu-

mor specimens (n =65), with a median of 378 mutations per

FIGURE 1 (A) Sensitivity and speciﬁcity of ctDNA monitoring in blood plasma and CSF using PhasED‐Seq. Grey bars on the left:

sensitivities copmpared to previous NGS‐based technologies (Fontanilles et al., Oncotarget 2017, Yoont et al., ASH Annual Meeting 2019,

Montesinos‐Rongen et al., J Mol Diagn 2020, Hattori et al., Cancer Sci 2018). Grey bars on the right show sensitivities of ﬂow cytometry (FC)

and Cytopathology (CP) in our cohort. (B) Scatter plot showing the comparision of ctDNA concentrations in pretreatment blood plasma and

CSF. (C) Correlation of Association between pretreatment ctDNA plasma concentrations and total radiographic tumor volume (TRTV)

measured by MRI. (D) ctDNA concentrations and steroid treatment at blood draw. (F) Kaplan Meier analysis of PFS and OS in patients with

detactabe and non‐detectable pretreatment ctDNA at diagnosis or progression. (G) Kaplan Meier analysis of PFS in patients with positive or

negative ctDNA during curative intent induction treatment

SUPPLEMENT ABSTRACTS

patient. Pretreatment plasma ctDNA was detectable in 82% of

patients and in 100% of CSF samples (Fig. 1A), with ctDNA con-

centrations ranging from 0.013‐1038 hGE/mL (median: 0.97) in

plasma and 0.043‐4342 hGE/mL (median: 3.55) in CSF (Fig. 1B).

While ctDNA levels were signiﬁcantly correlated with total tumor

volume in MRI (p =0.004, Fig. 1C), we did not observe signiﬁcant

associations between ctDNA levels and MSKCC score or concur-

rent steroid treatment (Fig. 1D‐E). Pretreatment ctDNA was

signiﬁcantly associated with PFS (p =0.0005, HR 3.6) and OS (p =

0.019, HR 3.1), both as continuous and binary variable (Fig. 1F).

Furthermore, ctDNA positivity during curative intent induction

therapy accurately predicted clinical outcomes (Fig. 1G). Finally, we

applied our novel machine learning classiﬁer to 129 specimens

from an independent validation cohort. We observed high speci-

ﬁcity (100%) and positive predictive value (100%) for noninvasive

diagnosis of CNSL, with moderate sensitivity (50% for CSF, 20%

for plasma), suggesting that a signiﬁcant subset of CNSL patients

might be able to forego invasive biopsies.

Conclusions: We demonstrate robust and ultrasensitive detection of

ctDNA at various disease milestones in PCNSL. Our ﬁndings suggest

that ctDNA could serve as a valuable clinical biomarker for tumor

burden assessment, outcome prediction, and biopsy‐free lymphoma

classiﬁcation. We envision an important future role of ctDNA for

personalized risk stratiﬁcation and guiding therapies in clinical trials

and in routine PCNSL management.

The research was funded by: the Else Kröner‐Fresenius‐Stiftung (to

FS, 2018_A83), the Fördergesellschaft Forschung Tumorbiologie (to

FS), and the Clinician Scientist Program of the Deutsche Gesellschaft

für Innere Medizin (to FS)

Keywords: Diagnostic and Prognostic Biomarkers, Liquid biopsy,

Extranodal non‐Hodgkin lymphoma

Conﬂicts of interests pertinent to the abstract

D. M. Kurtz

Consultant or advisory role: Roche Molecular Diagnostics,

Genentech

Other remuneration: Ownership equity in Foresight Diagnostics. Dr.

Kurtz has patents pending related to methods for analysis of cell free

nucleic acids and methods for treatment selection based on statistical

frameworks of clinical outcome.

M. Diehn

Consultant or advisory role: Roche, AstraZeneca, ReﬂeXion and

BioNTech

Research funding: Varian Medical Systems, Illumina

Other remuneration: Ownership interest in CiberMed, patent ﬁlings

related to cancer biomarkers

A. A. Alizadeh

Consultant or advisory role: Genentech, Roche, Chugai, Gilead,

Celgene

Other remuneration: Ownership interest in CiberMed and FortyS-

even Inc, patent ﬁlings related to cancer biomarkers.

047 |MATRIX INDUCTION FOLLOWED BY AUTOLOGOUS

STEM CELL TRANSPLANT OR WHOLE‐BRAIN IRRADIATION IN

PRIMARY CNS LYMPHOMA. 7‐YEAR RESULTS OF THE IELSG32

RANDOMIZED TRIAL

A. J. M. Ferreri

, K. Cwynarski

, E. Jacobsen Pulczynski

, C. Fox

E. Schorb

, C. Celico

, M. Falautano

, A. Nonis

, P. La Rosée

M. Binder

, A. Fabbri

, F. Ilariucci

, M. Krampera

, A. Röth

C. Hemmaway

, P. W. Johnson

, K. M. Linton

, T. Pukrop

J. Sønderskov Gørløv

, M. Balzarotti

, G. Hess

, U. Keller

S. Stilgenbauer

, J. Panse

, A. Tucci

, L. Orsucci

, F. Pisani

M. Zanni

, S. Krause

, H. J. Schmoll

, B. Hertenstein

M. Rummel

, J. Smith

, L. Thurner

, M. G. Cabras

, E. Pennese

M. Ponzoni

, M. Deckert

, L. S. Politi

, Jür. Finke

, A. Ferranti

K. Cozens

, E. Burger

, N. Ielmini

, F. Cavalli

, E. Zucca

G. Illerhaus

IRCCS San Raffaele Scientiﬁc Institute, Unità Operativa di Oncologia

Medica, Milano, Italy,

University College London Hospitals NHS Trust,

Department Of Haematology Royal Free Hospital, London, UK,

Aarhus

University Hospital, Department of Haematology, Aarhus, Denmark,

Nottingham University Hospitals NHS Trust, Clinical Haematology City

Campus, Nottingham, UK,

Universitätsklinikum Freiburg, Klinik für

INnere Medizin I, Freiburg, Germany,

IRCCS San Raffaele Scientiﬁc

Institute, Unità di Neuroriabilitazione, Milano, Italy,

IRCCS San Raffaele

Scientiﬁc Institute, Institute of Experimental Neurology, Milano, Italy,

IRCCS San Raffaele Scientiﬁc Institute, University Centre for Statistics in

the Biomedical Sciences, Milano, Italy,

Schwarzwald‐Baar Klinikum, Kli-

nik für Innere Medizin II, Villingen‐Schwenningen, Germany,

Uni-

versitätskrankenhaus Hamburg‐Eppendorf ‐UKE, Zentrum für Onkologie,

Hamburg, Germany,

Azienda Ospedaliera Universitaria Senese, UOC

Ematologia e Trapianti, Siena, Italy,

Azienda Ospedaliera di Reggio

Emilia, Arcispedale Santa Maria Nuova ‐Ematologia, Reggio Emilia, Italy,

Policlinico G.B. Rossi, Divisione di Ematologia, Verona, Italy,

Uni-

versitätsmedizin Essen, Westdeutsches Tumorzentrum Essen, Essen, Ger-

many,

Queen's Hospital, Hematology, Romford, UK,

Cancer Research

UK Centre, Southampton General Hospital, Southampton, UK,

Univer-

sity of Manchester, The Christie NHS Foundation Trust, Manchester, UK,

Georg‐August‐Universität Göttingen, Hämatologie und Oncologie, Göt-

tingen, Germany,

Rigshospitalet, Department of Hematology ‐4042,

Copenhagen, Sweden,

Istituto Clinico Humanitas, U.O. Oncologia

Medica ed Ematologia, Milano Rozzano, Italy,

Universitätsmedizin

Mainz, III Medizinische Klinik und Poliklinik, Mainz, Germany,

Techni-

sche Universität München, III. Medizinischen Klinik des Klinikums rechts

der Isar, München, Germany,

Universitätsklinikum Ulm, Klinik für innere

Medizin, Ulm, Germany,

Universitätsklinikum Aachen, Klinik für Innere

Medizin IV ‐Hämatologie/Onkologie, Aachen, Germany,

Spedali Civili,

SC Ematologia, Brescia, Italy,

A.O.U. Città della Salute e della Scienza di

Torino, Dipartimento di Oncologia ed Ematologia, Torino, Italy,

Istituto

Regina Elena, SC Ematologia, Roma, Italy,

Azienda Ospedaliera Nazio-

nale SS. Antonio e Biagio e C. Arrigo, SC Ematologia, Alessandria, Italy,

Universitätsklinikum Erlangen, Medizinische Klinik 5, Erlangen, Ger-

many,

Martin‐Luther Universität, Klinik für Hämatologie/Onkologie,

SUPPLEMENT ABSTRACTS

Halle, Germany,

Klinikum Bremen‐Mitte GmbH, Medizinische Klinik I,

Bremen, Germany,

Klinikum der Justus‐Liebing‐Universität, Klinikum

der Justus‐Liebing‐Universität Medizinische Klinik IV, Giessen, Germany,

Aintree University Hospital NHS FoundationTrust, Hematology, Liver-

pool, UK,

Universitätsklinikum des Saarlandes, Innere Medizin I, Hom-

burg, Germany,

Ospedale A. Businco, Unità Operativa di Ematologia,

Cagliari, Italy,

Presidio Ospedaliero Spirito Santo, Centro diagnosi e

terapia dei linfomi, Pescara, Italy,

IRCCS San Raffaele Scientiﬁc Insti-

tute, Haematopathology Diagnostic Area, Milano, Italy,

University of

Cologne, Department of Neuropathology, Köln, Germany,

IRCCS San

Raffaele Scientiﬁc Institute, Neuroradiology research, Milano, Italy,

Universitätsklinikum Freiburg, Klinik für Innere Medizin I, Freiburg,

Germany,

Fondazione Italiana Linfomi, Alessandria, Italy,

University

of Southampton, Clinical Trials Unit, Southampton, UK,

Uni-

versitätsklinikum Freiburg, Projektkoordination Klinische Studien, Frei-

burg, Germany,

Foundation for the Institute of Oncology Research (IOR),

International Extranodal Lymphoma Study Group, Bellinzona, Switzerland,

Foundation for the Institute of Oncology Research (IOR), International

Extranodal Lymphoma Study Group, Oncology Institute of Southern

Switzerland, Medical Oncology Clinic, Bellinzona, Switzerland,

Stuttgart

Cancer Centre (SCC), Clinic for Hematology and Internistisc Oncology,

Stuttgart, Germany

Introduction: The MATRix regimen (methotrexate, cytarabine, thio-

tepa, rituximab) signiﬁcantly improved outcome of patients (pts) with

primary CNS lymphoma (PCNSL) enrolled in the IELSG32 trial. At a

median follow‐up of 40 months, both whole‐brain irradiation (WBRT)

and autologous transplantation (ASCT) resulted in similar

progression‐free survival (PFS) rates. Sound assessment of overall

survival (OS), late complications, incidence of secondary tumors, and

cognitive impairment require, however, longer follow‐up. Herein, we

report the results of this trial at a median follow‐up of 88 (IQR 77‐99)

months.

Methods: HIV‐negative pts aged 18‐70 years with newly diagnosed

PCNSL were randomly assigned to receive 4 courses of

methotrexate‐cytarabine (arm A), or arm A plus rituximab (arm B), or

arm B plus thiotepa (MATRix; arm C). A second randomization allo-

cated pts with responsive/stable disease to WBRT (arm D) or car-

mustine ‐thiotepa conditioning followed by ASCT (arm E). Treatment

effect on cognitive functions and quality of life (QoL) was addressed

using the IPCG tests panel and EORTC‐QLQ.

Results: 219 assessable pts were randomized (arm A 75; B 69; C

75). After induction, 167 had responsive or stable disease; 118

were assigned to WBRT (59) or ASCT (59) while 49 were excluded

from second randomization (poor mobilizers, poor conditions,

refusal). Fifteen pts died of toxicity during treatment. Of 87 (40%)

relapse‐free pts (A 17; B 28; C 42), 14 died of infections (4),

sudden death (4), cognitive decline (3), second tumor (2) and car

accident (1). Among 117 pts with relapse, 96 died of lymphoma, 7

died of salvage therapy complications. Eight pts developed second

cancers 48‐96 months after WBRT (5) or ASCT (3). Second tumors,

deaths in relapse‐free pts and deaths during salvage therapy were

not signiﬁcantly related to induction or consolidation treatments.

Neuropsychological tests showed a statistically signiﬁcant impair-

ment in attentiveness and executive functions in pts treated with

WBRT, while transplanted pts had a signiﬁcant improvement in

these functions as well as in memory and QoL. Pts treated with

MATRix (arm C) showed signiﬁcantly better PFS (7‐year: 52% vs

20% for arm A; vs 29% for arm B) and OS rates (7‐year: 56% vs

26% for arm A; vs 37% for arm B). No signiﬁcant difference was

seen between the consolidation arms for either PFS (7‐year: 55%

for arm D vs 50% for arm E) or OS (7‐year: 63% vs 57%). Pts

treated with MATRix induction and consolidation had a 7‐year OS

of 70%, without a signiﬁcant difference between WBRT and ASCT.

IELSG score, number of lesions and induction arm were indepen-

dent predictors of OS.

Conclusions: MATRix regimen was associated with an excellent long‐

term outcome. WBRT and ASCT had comparable efﬁcacy. MATRix

and ASCT did not result in higher non‐relapse mortality or second

tumors incidence in comparison to the other study arms, whereas

WBRT led to impairment of speciﬁc cognitive functions.

EA ‐previously submitted to EHA 2021.

The research was funded by: IELSG32 was supported in part by

grants from Agenzia Italiana del Farmaco (Ricerca Indipendente

FARM99FS3Y), Oncosuisse (KLS 02399‐02‐2009), Swiss National

Science Foundation (31003B_132924) and Cancer Research UK

C36711/A12115). Adienne kindly supplied thiotepa for the treat-

ment of patients registered in the UK

SUPPLEMENT ABSTRACTS

Keywords: Chemotherapy Combination, Therapies Immunotherapy

Conﬂicts of interests pertinent to the abstract

A. J. M. Ferreri

Consultant or advisory role: Adienne, Gilead, Novartis, Juno,

PLetixaPharm

Research funding: BMS, Beigine, Pharmacyclics, Hutchison Medi-

pharma, Amgen, Genmab, ADC Therapeutics, Gilead, Novartis,

Pﬁzer

K. Cwynarski

Consultant or advisory role: Roche

Honoraria: Roche

Educational grants: Roche

E. Jacobsen Pulczynski

Research funding: Roche

C. Fox

Consultant or advisory role: Abbvie, AstraZeneca, Atarabio, BMS/

Celgene, Gilead, Jansen, Incyte, Roche, Takeda

Honoraria: Abbvie, Atarabio, BMS/Celgene, Jansen, Incyte, Roche,

Takeda

Research funding: Abbvie, Gilead, Roche, Takeda

Educational grants: Abbvie, BMS/Celgene, Janssen, Roche, Takeda

E. Schorb

Honoraria: Riemser Pharma GmbH

Research funding: Riemser Pharma GmbH

K. M. Linton

Consultant or advisory role: Genmab ‐Celgene ‐Kite/Gilead

Honoraria: Janssen

Research funding: Roche ‐Karyopharm

Educational grants: Janssen

U. Keller

Consultant or advisory role: Roche

Educational grants: Roche

S. Stilgenbauer

Consultant or advisory role: AbbVie, Amgen., AstraZeneca, Celgene,

Gilead, GSK, Hoffmann‐La‐Roche, Janssen, Novartis

Honoraria: AbbVie, Amgen., AstraZeneca, Celgene, Gilead, GSK,

Hoffmann‐La‐Roche, Janssen, Novartis

Research funding: AbbVie, Amgen., AstraZeneca, Celgene, Gilead,

GSK, Hoffmann‐La‐Roche, Janssen, Novartis

J. Smith

Educational grants: Grant provided to attend 15‐ICML by Janssen,

but arranged by Janssen (no payment)

L. Thurner

Consultant or advisory role: Merck, EUSA‐Pharma, Takeda

Educational grants: EUSA‐Pharma, Janssen, Abbvie

J. Finke

Honoraria: Riemser

Research funding: Riemser

G. Illerhaus

Honoraria: Riemser

Educational grants: Riemser

048 |INTENSIFIED (INTRAVENOUS AND INTRATHECAL) CNS

PROPHYLAXIS IN PRIMARY TESTICULAR DIFFUSE LARGE B‐CELL

LYMPHOMA: 5‐YEAR RESULTS OF THE IELSG30 TRIAL

A. Conconi

, A. Chiappella

, L. Orsucci

, G. Gaidano

, Andrés J.M.

Ferreri

, M. Balzarotti

, A. Tucci

, B. Botto

, A. Moccia

, A. Vanazzi

F. Merli

, M. Tani

, F. Esposito

, L. Bonomini

, U. Vitolo

E. Zucca

Azienda sanitaria locale Biella, Ospedale degli Infermi ‐Ematologia,

Biella, Italy,

A.O.U. Città della Salute e della Scienza di Torino,

Dipartimento di Oncologia ed Ematologia, Torino, Italy,

Azienda

Ospedaliera "Maggiore della Carità", Ematologia, Novara, Italy,

IRCCS

San Raffaele Scientiﬁc Institute, Unità Operativa di Oncologia Medica,

Milano, Italy,

Istituto Clinico Humanitas, U.O. Oncologia Medica ed

Ematologia, Milano Rozzano, Italy,

Spedali Civili, SC Ematologia, Brescia,

Italy,

Oncology Institute of Southern Switzerland, Medical Oncology

Clinic, Bellinzona, Switzerland,

Istituto Europeo di Oncologia,

Oncoematologia, Milano, Italy,

Azienda Ospedaliera di Reggio Emilia,

Arcispedale Santa Maria Nuova ‐Ematologia, Reggio Emilia, Italy,

Ospedale Santa Maria delle Croci, Dipartimento di Oncologia ed

Ematologia, Ravenna, Italy,

Foundation for the Institute of Oncology

Research (IOR), International Extranodal Lymphoma Study Group,

Oncology Institute of Southern Switzerland, Medical Oncology Clinic,

Bellinzona, Switzerland,

Foundation for the Institute of Oncology

Research (IOR), International Extranodal Lymphoma Study Group,

Bellinzona, Switzerland,

Candiolo Cancer Institute FPO‐IRCCS, Onco-

logia Medica, Candiolo, Italy

Introduction: Primary diffuse large B‐cell lymphoma of the testis

(PTL) represents a unique condition characterized by high long‐

term risk of contralateral testis and central nervous system

(CNS) relapse (>30% at 15 years) in historical series (Zucca et al,

JCO 2002). Immunochemotherapy associated with intrathecal CNS

prophylaxis and contralateral testis radiotherapy (RT) improved

patient outcome, with a virtual elimination of contralateral re-

currences and signiﬁcant reduction (6% at 5 years) of CNS re-

lapses in the IELSG10 trial (Vitolo et al., JCO 2011). The

International Extranodal Lymphoma Study Group (IELSG), in

cooperation with the Italian Lymphoma Foundation (FIL), coordi-

nated the multicenter phase II IELSG30 study to assess activity

and feasibility of intensiﬁed CNS prophylaxis in combination with

chemoimmunotherapy and RT.

SUPPLEMENT ABSTRACTS

Patients and Methods: Patients with stage I‐II PTL were eligible.

Treatment consisted of 6 cycles of the standard R‐CHOP21

regimen (rituximab, cyclophosphamide, doxorubicin, vincristine

and prednisone every 21 days); 4 doses of intrathecal liposomal

cytarabine; 2 courses of intravenous (iv) intermediate‐dose meth-

otrexate (1.5 gr/m2) and RT (25‐30 Gy) to the contralateral testis.

The study was designed to demonstrate (80% power, a =.05) a

PFS improvement from 67% to 82% at 10 years (primary

endpoint).

Results: Fifty‐four patients (median age: 66 years, range: 37‐79

years) with untreated stage I (n =32) or II (n =22) PTL were

treated with R‐CHOP21, 53 received at least 3 doses of intra-

thecal CNS prophylaxis, 48 received at least one dose of iv

methotrexate and 50 received prophylactic RT. No unexpected

side effects were observed. At a median follow‐up of 5 years, 7

patients progressed and 7 died, with 5‐year PFS of 88% (95%CI,

74‐94%) and 5‐year OS of 92% (95%CI, 79%‐97%). No CNS re-

lapses occurred. In 4 cases, both nodal and extranodal relapses

were reported, the latter including the gastrointestinal tract and

the pleurae in the same patient, as well as, 1 patient each, the

kidneys, the spinal canal (extra‐axial) and the contralateral testis (9

years after RT). Two patients relapsed only at extranodal sites

(skin, adrenal gland), 1 had nodal relapse. Notably, 4 of 7 failures

were late relapses occurring after 6 to 10 years from treatment.

Causes of death were lymphoma (n =4), second cancer (n =1),

cerebral vasculopathy (n =1), unknown (n =1).

Conclusions: Deﬁnitive assessment of the primary endpoint will need

longer follow‐up. Thus far, comparison of these results with those of

the IELSG10 trial (5‐yr PFS, 88 vs 74%; 5‐yr OS, 92 vs 85%; 5‐yr CNS

relapse rate, 0 vs 6%) suggests that combined treatment of PTL with

R‐CHOP21 plus intensive CNS prophylaxis and loco‐regional RT is

feasible, may abrogate CNS relapses and lead to very promising

outcomes. Nevertheless, late relapses, mainly at extranodal sites, still

represent a clinical challenge.

The research was funded by: Mundipharma provided the drug

depocyte free of charge

Keywords: Combination Therapies, Radiation Therapy

Conﬂicts of interests pertinent to the abstract

A. J. M. Ferreri

Consultant or advisory role: Adienne ‐Gilead ‐Novartis ‐Juno ‐

PletixaPharm

Research funding: BMS ‐Beigene ‐Pharmacyclics ‐Hutchison ‐

Medipharma ‐Amgen ‐Genmab ‐ADC ‐Therapeutics ‐Gilead ‐

Novartis ‐Pﬁzer

E. Zucca

Consultant or advisory role: Beigene ‐Celgene ‐Incyte ‐Janssen ‐

Merck ‐Roche ‐Celltrion Healthcare ‐Kite (Gilead)

Research funding: AstraZeneca ‐Celgene ‐Incyte ‐Janssen ‐Merck ‐

Roche

Educational grants: Roche – Abbvie

049 |IMPACT OF DIFFERENT INDUCTION REGIMENS ON THE

OUTCOME OF PRIMARY MEDIASTINAL B CELL LYMPHOMA IN

THE PROSPECTIVE IELSG 37 TRIAL

M. Martelli

, E. Zucca

, B. Botto

, I. Kryachok

, L. Ceriani

M. Balzarotti

, A. Tucci

, M. G. Cabras

, V. R. Zilioli

, C. Rusconi

F. Angrilli

, L. Arcaini

, A. Dabrowska Iwanicka

, A. J. M. Ferreri

, F.

Merli

, W. Zhao

, D. Hodgson

, C. Ionescu

, A. Fosså

, K.

Cwynarski

, G. Mikhaeel

, M. Jerkeman

, A. Janikova

A. Hüttmann

, G. Ciccone

, U. Metser

, S. Barrington

B. Malkowski

, A. Versari

, F. Esposito

, K. Cozens

, N. Ielmini

U. Ricardi

, F. Cavalli

, P. Johnson

, A. Davies

Università La Sapienza, Dipartimento Biotecnologie Cellulari ed

Ematologia, Roma, Italy,

Foundation for the Institute of Oncology

SUPPLEMENT ABSTRACTS

Research (IOR), International Extranodal Lymphoma Study Group,

Oncology Institute of Southern Switzerland, Medical Oncology Clinic,

Bellinzona, Switzerland,

A.O.U. Città della Salute e della Scienza di

Torino, Dipartimento di Oncologia ed Ematologia, Torino, Italy,

National Cancer Institute, Oncohematology, Kyiv, Ukraine,

Institute of

Imaging of Southern Switzerland, Department of nuclear medicine and

PET/CT Centre, Lugano, Switzerland,

Istituto Clinico Humanitas, U.O.

Oncologia Medica ed Ematologia, Milano Rozzano, Italy,

Spedali Civili,

SC Ematologia, Brescia, Italy,

Ospedale Oncologico, Struttura

complessa di Ematologia e CTMO, Cagliari, Italy,

Azienda Ospedaliera

Ospedale Niguarda Ca’ Granda, Ematologia, Milan, Italy,

Lymphoma

Unit, Oncology and Hematology, Pescara, Italy,

I.R.C.C.S. Policlinico

San Matteo, Divisione di Ematologia, Pavia, Italy,

Maria Sklodowska‐

Curie Memorial Cancer Center, Department of lymphoid malignancies,

Warsaw, Poland,

IRCCS San Raffaele Scientiﬁc Institute, Unità

Operativa di Oncologia Medica, Milano, Italy,

Arcispedale Santa

Maria Nuova, Servizio di Ematologia, Reggio Emilia, Italy,

Rui Jin

Hospital, Hematology, Shanghai, China,

University Health Network,

Princess Margaret Hospital, Toronto, Canada,

Inselspital, Klinik und

Poliklinik für Medizinische Onkologie, Bern, Switzerland,

University

Hospital, Oncology, Oslo, Norway,

University College London Hospi-

tals NHS Trust, Department Of Haematology Royal Free Hospital,

London, UK,

Guy's & St. Thomas Hospital, Clinical Oncology, London,

UK,

University Hospital, Medical Oncology, Lund, Sweden,

Univer-

sity Hospital Brno‐Bohunice, Department of Internal Medicine, Hema-

tology and Oncology, Brno, Czech Republic,

Universitatsklinikum

Essen, Hematology, Essen, Germany,

AOU Città della Salute e della

Scienza di Torino (Molinette) e CPO, SSD Epidemiologia Clinica e

Valutativa, Torino, Italy,

St Thomas' Hospital, Nuclear Medicine,

London, UK,

Bydgoszcz Medical Center, Nuclear medicine,

Bydgoszcz1, Poland,

Arcispedale S. Maria Nuova, Nuclear Medicine,

Reggio Emilia, Italy,

University of Southampton, Clinical Trials Unit,

Southampton, UK,

Foundation for the Institute of Oncology Research

(IOR), International Extranodal Lymphoma Study Group, Bellinzona,

Switzerland,

Southampton General Hospital, Cancer Research UK

Centre, Southampton, UK,

Southampton General Hospital, Cancer

Sciences Division, Southampton, UK,

A.O.U. Città della Salute e della

Scienza di Torino, Sezione di Radioterapia, Dipartimento di Oncologia

ed Ematologia, Torino, Italy

Introduction: Primary mediastinal B‐cell lymphoma (PMBCL) is

characterized by poor prognosis if adequate responses are not

rapidly achieved or if the disease recurs. Therefore, dose‐intensive

chemoimmunotherapy regimens are widely used but their superi-

ority over the standard R‐CHOP21 regimen has not been proven

by randomized trials, furthermore they come with signiﬁcant

associated toxicities. Radiotherapy (RT) can consolidate responses

after induction, but it may increase the risk of second malignancies

and accelerate coronary heart disease. The IELSG37 trial was

planned according to a non‐inferiority design to demonstrate that

RT may be unnecessary in patients achieving a metabolic com-

plete remission. The primary‐endpoint analysis per arm will be

reported when >80% will have a minimum post‐treatment follow‐

up of 30 months. Herein we present a preliminary analysis of the

outcomes after different induction regimens in the whole study

population.

Methods: Patients with newly diagnosed PMBCL were eligible. Initial

therapy was to be based on a combination containing rituximab and

anthracyclines. The regimen was chosen according to local practice.

Upon central review of post‐induction PET scans, responding pa-

tients were randomized to observation versus consolidative RT. Re-

sponses were deﬁned according to the Lugano classiﬁcation using the

Deauville 5‐point scale (DS). Patients progressing during induction

did not have central PET review and in the present analysis were

assigned DS score 5.

Results: 545 patients (209 men, 336 women) were enrolled and

treated with R‐V/MACOP‐B (n =168, 31%), R‐CHOP14 (n =146,

27%), R‐CHOP21 (n =98, 18%), DA‐EPOCH‐R (n =88, 16%), R‐

megaCHOP (n =19, 3%), other dose‐intensive regimen (n =26,

5%). At a median follow up of 3 years, approx. 95% of patients are

SUPPLEMENT ABSTRACTS

alive. The rate of complete metabolic responses (CR, deﬁned by DS 1‐

3) did not differ signiﬁcantly across regimens, however an unbal-

anced distribution of DS score was evident, apparently due to the

rate of patients with a probable induction failure (DS5) more than 2

times higher for CHOP21 in comparison to the other regimens. At

preliminary univariate analysis there was no signiﬁcant association of

advanced stage, older age, extranodal inﬁltration, poor performance

status, bulky disease, unfavorable international prognostic index (IPI)

and larger metabolic tumor volume (MTV) with the use of CHOP21.

Patients receiving DA‐EPOCH‐R were somehow younger than the

rest.

Conclusion: Initial regimen may have critical impact on PMBCL

outcome. R‐CHOP21 appeared inferior to dose‐dense/dose‐intensive

regimens.

The research was funded by: IELSG37 was supported in part by

grants from Swiss National Science Foundation (SNSF) – Project

32003B_146931,Krebsforschung Schweiz – Projec KFS‐2852‐08‐

2011 and Cancer Research UK (C30423/A16247)The enrolment of

Swiss patients was supported by the Swiss Group for Clinical Cancer

Research (SAKK)

Keywords: Chemotherapy Combination, Therapies Immunotherapy

No conﬂicts of interests pertinent to the abstract.

050 |OUTCOMES AFTER FIRST‐LINE

IMMUNOCHEMOTHERAPY FOR PRIMARY MEDIASTINAL B CELL

LYMPHOMA PATIENTS: A LYSA STUDY

V. Camus

, C. Rossi

, P. Sesques

, J. Lequesne

, D. Tonnelet

C. Haioun

, E. Durot

, A. Willaume

, M. Gauthier

, Marie‐P. Moles‐

Moreau

, C. Antier

, J. Lazarovici

, H. Monjanel

, S. Bernard

M. Tardy

, C. Besson

, L. Lebras

, S. Choquet

, K. Le Du

C. Bonnet

, S. Bailly

, G.‐L. Damaj

, K. Laribi

, H. Maisonneuve

R. Houot

, A. Chauchet

, F. Jardin

, A. Traverse‐Glehen

P. Decazes

, S. Becker

, A. Berriolo‐Riedinger

, H. Tilly

Centre Henri Becquerel, Department of Hematology, Rouen, France,

Dijon University Hospital, Hematology, Dijon, France,

CHU Lyon Sud,

Hematology, Pierre‐Bénite, France,

Centre Henri Becquerel, Clinical

Research Unit, Rouen, France,

Centre Henri Becquerel, Department of

Nuclear Medicine, Rouen, France,

CHU Mondor, Hematology, Créteil,

France,

CHU Reims, Hematology, Reims, France,

CHU Lille,

Hematology, Lille, France,

IUCT Oncopole, Hematology, Toulouse,

France,

CHU Angers, Hematology, Angers, France,

CHU Nantes,

Hematology, Nantes, France,

Institut Gustave Roussy, Hematology,

Villejuif, France,

CH Aurillac, Hematology, Aurillac, France,

CHU St

Louis, Hematology, Paris, France,

Centre Antoine Lacassagne,

Hematology, Nice, France,

Centre Hospitalier de Versailles,

Hematology, Le Chesnay, France,

Centre Leon Berard, Hematology,

Lyon, France,

CHU La pitié salpetriere, Hematology, Paris, France,

Clinique Victor Hugo, Hematology, Le Mans, France,

Liege

University Hospital, Hematology, Liege, Belgium,

Cliniques

Universitaires Saint Luc, Hematology, Bruxelles, Belgium,

CHU Caen,

Hematology, Caen, France,

CH Le Mans, Hematology, Le Mans,

France,

CH Departemental de Vendée, Hematology, la Roche sur

Yon, France,

CHU Rennes, Hematology, Rennes, France,

Besançon, hematology, Besançon, France,

CHU Lyon Sud,

Pathology, Pierre‐Bénite, France,

CHU Dijon, Nuclear Medicine,

Dijon, France

Introduction: Primary mediastinal B‐cell lymphoma (PMBL) is a

rare subtype of aggressive lymphoma typically affecting young

female patients. The ﬁrst‐line standard of care remains debated.

Methods: We performed a large multicenter retrospective study in

25 centers in France and Belgium to describe PMBL patient out-

comes after ﬁrst‐line treatment in real‐life settings. All adult pa-

tients with newly diagnosed PMBL treated in France and Belgium

by participating Lymphoma Study Association (LYSA) centers from

01/01/2007 to 31/12/2017 were identiﬁed from local databases.

The inclusion criteria were as follows: ﬁrst‐line treatment with

ACVBP or CHOP plus anti‐CD20 monoclonal antibody, PET per-

formed at baseline and the patient's non‐opposition statement.

Primary endpoint was progression‐free survival (PFS) and second-

ary endpoints included overall survival (OS) and baseline total

metabolic tumor volume (TMTV) using the 41% SUVmax threshold

method.

Results: Three hundred thirteen patients were enrolled and

received rituximab (R) plus ACVBP (n =180) or CHOP delivered

every 14 (R‐CHOP14, n =76) or 21 days (R‐CHOP21, n =57)

and consolidation strategies in modalities that varied according to

time and institution, mainly guided by positron emission tomog-

raphy. Consolidation autologous stem cell transplantation was

performed for 46 (25.6%), 24 (31.6%) and one (1.8%) patients in

the R‐ACVBP, R‐CHOP14 and R‐CHOP21 groups, respectively (p

<0.001); only 17 (5.4%) patients received mediastinal radio-

therapy. The end‐of‐treatment complete metabolic response rates

were 86.3%, 86.8% and 76.6% (p =0.23) in the R‐ACVBP, R‐

CHOP14 and R‐CHOP21 groups, respectively. The median

follow‐up was 44 (1‐153) months, and the R‐ACVBP, R‐CHOP14

and R‐CHOP21 3‐year PFS and OS were 89.4% (84.8‐94.2%),

89.4% (82.7‐96.6%), and 74.7% (95% CI: 64‐87.1%), (p =0.018,

Figure 1A), respectively; and 92.4% (88.4‐96.7%), 100% (100‐

100%), and 87.5% (78.6‐97.6%), (p =0.0036, Figure 1B), respec-

tively. Baseline TMTV≥360 cm3 was associated with a lower

PFS (hazard ratio =2.18 [1.05‐4.53]). Excess febrile neutropenia

(24.4% vs 5.3% vs 5.3%, p <0.001) and mucositis (22.8% vs 3.9%

vs 1.8%, p <0.001) were observed with R‐ACVBP compared to R‐

CHOP regimens.

Conclusion: PMBL patients treated with dose‐dense immunoche-

motherapy without radiotherapy have excellent outcomes. R‐ACVBP

acute toxicity was higher than that of R‐CHOP14. Our data

conﬁrmed the prognostic importance of the baseline TMTV.

The research was funded by: grants from the Centre Henri Becquerel

and the Ligue Contre le Cancer (Comité de la Manche).

SUPPLEMENT ABSTRACTS

Keywords: Aggressive B‐cell non‐Hodgkin lymphoma

No conﬂicts of interests pertinent to the abstract.

051 |NIVOLUMAB PLUS BRENTUXIMAB VEDOTIN FOR

RELAPSED/REFRACTORY PRIMARY MEDIASTINAL LARGE B‐

CELL LYMPHOMA: EXTENDED FOLLOW‐UP FROM THE PHASE 2

CHECKMATE 436 STUDY

P. L. Zinzani

, A. Santoro

, G. Gritti

, P. Brice

, P. M. Barr

J. Kuruvilla

, D. Cunningham

, J. Kline

, N. A. Johnson

N. Mehta‐Shah

, M. Fanale

, S. Francis

, A. J. Moskowitz

“Seràgnoli" Bologna University, Institute of Hematology, Bologna, Italy,

IRCCS Humanitas Research Center, Humanitas University, Rozzano–

Milano, Italy,

Ospedale Papa Giovanni XXIII, Hematology and Bone

Marrow Transplant Unit, Bergamo, Italy,

Hôpital Saint‐Louis, Service

d’Hémato‐Oncologie, Paris, France,

University of Rochester, Depart-

ment of Medicine, Hematology/Oncology, Rochester, New York, USA,

Princess Margaret Cancer Centre, Division of Medical Oncology and

Hematology, Toronto, Canada,

Royal Marsden Hospital, Gastrointes-

tinal and Lymphoma Unit, London, UK,

University of Chicago,

Department of Medicine, Section of Hematology/Oncology, Chicago,

Illinois, USA,

Jewish General Hospital, Division of Hematology, Mon-

treal, Canada,

Washington University in St. Louis School of Medicine,

Division of Oncology, Department of Medicine, St. Louis, Missouri, USA,

Seagen Inc., Medical Affairs, Bothell, Washington, USA,

Bristol

Myers Squibb, Global Biometrics and Data Sciences, Princeton, New

Jersey, USA,

Memorial Sloan Kettering Cancer Center, Lymphoma

Inpatient Unit, New York, New York, USA

Introduction: Patients (pts) with relapsed/refractory (R/R) pri-

mary mediastinal B‐cell lymphoma (PMBL) have poor outcomes

and limited treatment options. PMBL is characterized by

increased programmed death‐1 (PD‐1) ligand expression and weak

CD30 expression. The combination of nivolumab (NIVO), an anti–

PD‐1 immune checkpoint inhibitor, and brentuximab vedotin

(BV), an anti‐CD30 antibody–drug conjugate, has been assessed

in pts with R/R PMBL in the open‐label, phase 1/2 CheckMate

436 study (NCT02581631); in the primary analysis (median

follow‐up [FU] 11.1 months) NIVO +BV showed an ORR of 73%

and complete remission (CR) rate of 37% (Zinzani et al. J

Clin Oncol 2019). We report efﬁcacy and safety data after

extended FU.

Methods: The expansion cohort of CheckMate 436 enrolled pts with

R/R PMBL after autologous hematopoietic cell transplantation (auto‐

HCT) or ≥2 prior multi‐agent chemotherapy regimens if ineligible for

auto‐HCT. Pts received NIVO (240 mg IV) +BV (1.8 mg/kg IV) every

3 weeks until disease progression or unacceptable toxicity. Primary

endpoints were investigator‐assessed ORR per Lugano 2014 criteria

and safety. Secondary endpoints were duration of response (DOR),

CR rate, duration of CR, progression‐free survival (PFS), and overall

survival (OS).

Results: Among 30 pts, median age was 35.5 years. At a median

FU of 33.7 months, ORR was 73% (95% CI, 54–88) and CR rate

was 37%. Median DOR was 31.6 months (95% CI, 23.3–not

estimable [NE]) and median duration of CR was not reached (95%

CI, 27.9–NE) The Kaplan–Meier estimate of median PFS was 26.0

months (95% CI, 2.6–NE; Figure). Among the 17 censored pts in

the PFS analysis, 13 received consolidation therapy, including

FIGURE 1 Progression‐free survival (PFs) and Overall Survival (OS) according to ACVBP, CHOP14 and CHOP21 plus anti‐CD20

treatment groups

SUPPLEMENT ABSTRACTS

auto‐HCT (n =6) or allogeneic‐HCT (n =6) with or without

radiotherapy (RT), and RT alone (n =1); of pts with assessments

1 year after auto‐HCT and allo‐HCT, 5/6 and 5/5 had CR,

respectively. Four pts remained progression‐free in FU for 137+,

273+, 372+, and 606+days after discontinuation of NIVO +BV

(3 due to maximum clinical beneﬁt and 1 due to study drug

toxicity) without receiving subsequent therapy. The OS rate was

79% (95% CI, 59–90) at 12 months and 76% (95% CI, 55–88) at

24 months; median OS was not reached. Any‐grade treatment‐

related adverse events (TRAEs) occurred in 83% of pts, most

frequently neutropenia (30%; all grade 3–4) and peripheral neu-

ropathy (27%; 10% grade 3–4). TRAEs led to discontinuation in 6

pts. No graft‐versus‐host disease was reported in the 6 pts

receiving subsequent allo‐HCT. There were 8 deaths, 5 due to

disease progression and none considered related to study drug

toxicity.

Conclusions: In this extended FU of CheckMate 436, NIVO +BV

demonstrated durable responses and long‐term survival beneﬁts;

4 pts remained progression‐free without consolidation after NIVO

+BV. Safety was consistent with prior ﬁndings. These results

further support NIVO +BV as a treatment option for pts with R/R

PMBL.

The research was funded by: Bristol Myers Squibb

Keywords: Aggressive B‐cell non‐Hodgkin lymphoma, Combination

Therapies, Immunotherapy

Conﬂicts of interests pertinent to the abstract

P. L. Zinzani

Consultant or advisory role: Servier, Merck, Janssen, Eusapharma,

Takeda, Incyte, Gilead, Novartis

Honoraria: Servier, Merck, Janssen, Eusapharma, Takeda, Incyte,

Gilead, Novartis

A. Santoro

Consultant or advisory role: Bristol Myers Squibb, Servier, Gilead,

Pﬁzer, Eisai, Bayer, Merck Sharp & Dohme, Arqule, Sanoﬁ

Other remuneration: Takeda, Bristol Myers Squibb, Roche, AbbVie,

Amgen, Celgene, Servier, Gilead, AstraZeneca, Pﬁzer, Arqule, Lilly,

Sandoz, Eisai, Novartis, Bayer, Merck Sharp & Dohme

G. Gritti

Consultant or advisory role: Takeda, IQvia, Gilead Sciences

Honoraria: Amgen, Roche

Research funding: Gilead Sciences

Educational grants: Roche, Abbvie, Gilead Sciences, Abbvie

P. Brice

Honoraria: MDS, Takeda

P. M. Barr

Consultant or advisory role: Bristol Myers Squibb, AbbVie, Janssen,

Genentech, TG therapeutics, Gilead, Merck, Morphosys, Bayer,

Seattle Genetics, Beigene, MEI

J. Kuruvilla

Consultant or advisory role: AbbVie, Bristol Myers Squibb, Gilead,

Karyopharm, Merck, Roche, Seattle Genetics

Honoraria: Amgen, Antengene, Astra Zeneca, Bristol Myers Squibb,

Gilead, Incyte, Janssen, Karyopharm, Merck, Novartis, Pﬁzer, Roche,

Seattle Genetics, TG Therapeutics

Research funding: Canadian Cancer Society, Leukemia and Lym-

phoma Society Canada, Princess Margaret Cancer Foundation,

Janssen, Roche, AstraZeneca

Other remuneration: Karyopharm (DSMB)

D. Cunningham

Consultant or advisory role: OVIBIO on Scientiﬁc Advisory Board

Research funding: Amgen, Sanoﬁ, Merrimack, AstraZeneca, Celgene,

MedImmune, Bayer, 4SC, Clovis, Eli Lilly, Janssen, Merck

J. Kline

Consultant or advisory role: Merck

Honoraria: Kite/Gilead, MorphoSys, Karyopharm, Verastem, Seagen

Research funding: Merck, iTeos, Verastem

N. A. Johnson

Consultant or advisory role: Merck, Bristol Myers Squibb, Roche,

Seattle Genetics, AbbVie, Jansson, Gilead

Honoraria: Roche

Research funding: AbbVie, Roche

N. Mehta‐Shah

Consultant or advisory role: Kiowa Hakka Kirin, Karyopharm Ther-

apeutics, C4 Therapeutics, Daiichi Sankyo, Ono Pharmaceuticals,

Secura Bio

Research funding: Bristol Myers Squibb, Celgene, Verastem, Innate

Pharmaceuticals, Corvus Pharmaceuticals, Genentech/Roche

M. Fanale

Employment or leadership position: Seattle Genetics

Stock ownership: Seattle Genetics

S. Francis

Employment or leadership position: Bristol Myers Squibb

Stock ownership: Bristol Myers Squibb

Progression‐free survival

SUPPLEMENT ABSTRACTS

A. J. Moskowitz

Honoraria: Imbrium Therapeutics L.P., Merck, and Seattle Genetics

Research funding: Miragen, Seattle Genetics, Merck, Bristol Myers

Squibb, and Incyte

SESSION 8: PERIPHERAL T/NK‐CELL LYMPHOMAS

052 |ESA VERSUS MESA WITH SANDWICHED

RADIOTHERAPY IN PATIENTS WITH EARLY‐STAGE NATURAL

KILLER/T‐CELL LYMPHOMA: A MULTICENTRE, RANDOMISED,

PHASE 3, NON‐INFERIORITY TRIAL

H.‐J. Zhong

, S. Cheng

, X. Zhang

, B. Xu

, J.‐Y. Chen

, X.‐F. Jiang

Y. Hu

, G.‐H. Cui

, J.‐Y. Wei

, W.‐B. Qian

, X.‐B. Huang

, M. Hou

F. Yan

, X. Wang

, Y.‐P. Song

, J.‐D. Hu

, Y.‐H. Liu

, X.‐J. Ma

F. Li

, C.‐Y. Wu

, J.‐M. Chen

, L. Yu

, O. Bai

, J.‐Y. Xu

, Zun‐M.

Zhu

, L. Liu

, X. Zhou

, L. Huang

, Y. Tong

, T. Niu

, D.‐P. Wu

J. Xiong

, H. Zhang

, C.‐F. Wang

, B. Ouyang

, H.‐M. Yi

G. Cai

, B. Li

, J. Liu

, Z.‐F. Li

, R. Xiao

, L.‐Q. Wang

Y.‐J. Jiang

, Y.‐Y. Liu

, X.‐Y. Zheng

, P.‐P. Xu

, H.‐Y. Huang

L. Wang

, S.‐J. Chen

, W.‐L. Zhao

Ruijin Hospital Afﬁliated to Shanghai Jiao Tong University School of

Medicine, Department of Hematology, Shanghai, China,

Ruijin Hospital

Afﬁliated to Shanghai Jiao Tong University School of Medicine,

Department of Hematology, Shanghai, China,

Xinqiao Hospital,

Department of Hematology, Chongqing, China,

First Afﬁliated Hospital

of Xiamen University, Department of Hematology, Xiamen, China,

Ruijin Hospital Afﬁliated to Shanghai Jiao Tong University School of

Medicine, Department of Radiation Oncology, Shanghai, China,

Ruijin

Hospital Afﬁliated to Shanghai Jiao Tong University School of Medicine,

Department of Nuclear Medicine, Shanghai, China,

Union Hospital,

Tongji Medical College, Huazhong University of Science and Technology,

Institute of Hematology, Wuhan, China,

Union Hospital, Tongji Medical

College, Huazhong University of Science and Technology, Institute of

Hematology, Wuhan, China,

First Afﬁliated Hospital of Zhejiang

University School of Medicine, Department of Hematology, Hangzhou,

China,

Second Afﬁliated Hospital of Zhejiang University School of

Medicine, Department of Hematology, Hangzhou, China,

Sichuan

Provincial People's Hospital, Department of Hematology, Chengdu,

China,

Qilu Hospital, Shandong University, Department of

Hematology, Jinan, China,

First People's Hospital of Changzhou,

Department of Hematology, Changzhou, China,

Shandong Provincial

Hospital Afﬁliated to Shandong University, Department of Hematology,

Jinan, China,

Afﬁliated Cancer Hospital of Zhengzhou University,

Department of Hematology, Zhengzhou, China,

Fujian Medical

University Union Hospital, Department of Hematology, Fuzhou, China,

Jiangsu Cancer Hospital, Department of Medical Oncology, Nanjing,

China,

Shanghai Cancer Center, Fudan University, Department of

Medical Oncology, Shanghai, China,

First Afﬁliated Hospital of

Nanchang University, Department of Hematology, Nanchang, China,

Second Hospital of Lanzhou University, Department of Hematology,

Lanzhou, China,

First Afﬁliated Hospital of Fujian Medical University,

Department of Hematology and Rheumatology, Fuzhou, China,

The

Second Afﬁliated Hospital of Nanchang University, Department of

Hematology, Nanchang, China,

First Hospital of Jilin University,

Department of Hematology, Jilin, China,

Nanjing Drum Tower

Hospital, Department of Hematology, Nanjing, China,

Henan Province

People's Hospital, Department of Hematology, Zhengzhou, China,

Tangdu Hospital, Department of Hematology, Xi'an, China,

Wuxi

People's Hospital Afﬁliated to Nanjing Medical University, Department

of Hematology, Wuxi, China,

Hospital (T.C.M) Afﬁliated to Southwest

Medical University, Department of Oncology and Hematology, Luzhou,

China,

Shanghai General Hospital Afﬁliated to Shanghai Jiao Tong

University, Department of Hematology, Shanghai, China,

West China

Hospital, Sichuan University, Department of Hematology, Chengdu,

China,

First Afﬁliated Hospital of Soochow University, Institute of

Hematology, Suzhou, China,

Ruijin Hospital Afﬁliated to Shanghai

Jiao Tong University School of Medicine, Department of Hematology,

Shanghai, China,

Ruijin Hospital Afﬁliated to Shanghai Jiao Tong

University School of Medicine, Department of Otolaryngology, Shanghai,

China,

Ruijin Hospital Afﬁliated to Shanghai Jiao Tong University

School of Medicine, Department of Pathology, Shanghai, China,

Ruijin

Hospital Afﬁliated to Shanghai Jiao Tong University School of Medicine,

Department of Pathology, Shanghai, China,

Ruijin Hospital Afﬁliated

to Shanghai Jiao Tong University School of Medicine, Department of

Pathology, Shanghai, China,

Ruijin Hospital Afﬁliated to Shanghai

Jiao Tong University School of Medicine, Department of Radiation

Oncology, Shanghai, China,

Ruijin Hospital Afﬁliated to Shanghai Jiao

Tong University School of Medicine, Department of Nuclear Medicine,

Shanghai, China,

Xinqiao Hospital, Department of Hematology,

Chongqing, China,

First Afﬁliated Hospital of Xiamen University,

Department of Hematology, Xiamen, China,

Sichuan Provincial

People's Hospital, Department of Hematology, Chengdu, China,

Qilu

Hospital, Shandong University, Department of Hematology, Jinan,

China,

Shandong Provincial Hospital Afﬁliated to Shandong

University, Department of Hematology, Jinan, China,

Afﬁliated Cancer

Hospital of Zhengzhou University, Department of Hematology,

Zhengzhou, China,

Fujian Medical University Union Hospital,

Department of Hematology, Fuzhou, China,

Ruijin Hospital Afﬁliated

to Shanghai Jiao Tong University School of Medicine, Department of

Hematology, Shanghai, China,

Shanghai Jiao Tong University School

of Medicine, School of Public Health, Shanghai, China,

Ruijin Hospital

Afﬁliated to Shanghai Jiao Tong University School of Medicine,

Department of Hematology, Shanghai, China,

Shanghai Institute of

Hematology, State Key Laboratory of Medical Genomics, National

Research Center for Translational Medicine at Shanghai, Ruijin Hospital

Afﬁliated to Shanghai Jiao Tong University School of Medicine,

Department of Hematology, Shanghai, China,

Shanghai Institute of

Hematology, State Key Laboratory of Medical Genomics, National

Research Center for Translational Medicine at Shanghai, Ruijin Hospital

Afﬁliated to Shanghai Jiao Tong University School of Medicine,

Department of Hematology, Shanghai, China

SUPPLEMENT ABSTRACTS

Background: Natural killer/T‐cell lymphoma (NKTL) is a highly

aggressive lymphoma that usually treated with intensive chemo-

therapy. Our phase 2 study showed that methotrexate, etoposide,

dexamethasone, pegaspargase (MESA) regimen with sandwiched

radiotherapy was safe and effective for early‐stage NKTL. However,

it is unclear whether intensity of chemotherapy can be further

reduced for early‐stage NKTL in the era of asparaginase with sand-

wiched radiotherapy.

Methods: We conducted a multicentre, randomised, phase 3 non‐

inferiority trial involving patients aged 14‐70 years with newly

diagnosed early‐stage NKTL from 27 centres of the Multicenter

Hematology‐Oncology Programs Evaluation System in China. Ran-

domisation was computer‐assisted with a block size of four. In-

vestigators and patients were not masked to treatment

assignment. Patients were randomly assigned in a 1:1 ratio to

receive four cycles of low‐intensity ESA (pegaspargase, oral eto-

poside and dexamethasone) with sandwiched radiotherapy or four

cycles of MESA with sandwiched radiotherapy. The primary end

point was overall response rate. A non‐inferiority margin of ‐10.0%

was designed for ESA with sandwiched radiotherapy versus MESA

with sandwiched radiotherapy. The primary and safety analysis

were performed in the modiﬁed intention‐to‐treat population

including patients who received at least one cycle of assigned

treatment. The trial was prospectively registered at ClinicalTrials.

gov, NCT02631239.

Findings: Between March 16, 2016, and July 17, 2020, a total of 256

patients were enrolled, and 248 (125 of ESA with sandwiched

radiotherapy and 123 of MESA with sandwiched radiotherapy) made

up the modiﬁed intention‐to‐treat population. The overall response

rate was 88.8% (95% conﬁdence interval [CI] 83.2‐94.4) in the ESA

with sandwiched radiotherapy group and 86.2% (80.0‐92.4) in the

MESA with sandwiched radiotherapy group, with an absolutely rate

difference of 2.6 percentage points (‐3.6‐8.8). The lower limit of the

95%CI for the absolute rate difference is within the designated non‐

SUPPLEMENT ABSTRACTS

inferiority margin. Per‐protocol analysis and sensitivity analysis

supported this result. Adverse events of grade 3 or higher occurred

in 42 (33.6%) of the patients with ESA with sandwiched radiotherapy

and 81 (65.9%) with MESA with sandwiched radiotherapy. Three

patients in the ESA with sandwiched radiotherapy group died due to

adverse events. Five patients in the MESA with sandwiched radio-

therapy group died due to adverse events.

Interpretation: Low‐intensity ESA with sandwiched radiotherapy is

highly effective and non‐intravenous treatment, with low toxicity and

outpatient basis, and can be considered as ﬁrst‐line treatment option

in newly diagnosed early‐stage NKTL.

Keywords: Combination Therapies

No conﬂicts of interests pertinent to the abstract.

053 |ALLOGENEIC HEMATOPOIETIC CELL

TRANSPLANTATION FOR PERIPHERAL T‐CELL LYMPHOMA:

COMPARABLE OUTCOMES OF HAPLO‐IDENTICAL VS. MATCHED

DONORS. A CIBMTR & EBMT ANALYSIS

P. Dreger

, M. Ngoya

, C. Litovich

, H. Finel

, A. F Herrera

C. Sauter

, M. Kharfan‐Dabaja

, A. Sureda

, D. Blaise

, L. Castagna

P. Corradini

, R. Pastano

, M. Arat

, A. Boumendil

, S. Dietrich

N. Schmitz

, B. Glass

, S. Montoto

, M. Hamadani

EBMT, Lymphoma Working Party, Paris, France,

CIBMTR, Lymphoma

Working Committee, Milwaukee, Wisconsin, USA

Introduction: The advent of immunosuppression with post‐

transplant cyclophosphamide (ptCY) has facilitated allogeneic he-

matopoietic cell transplantation (alloHCT) from haplo‐identical do-

nors in patients lacking a matched donor. The aim of this study was to

compare the outcomes of ptCY haplo‐identical transplantation

(haploHCT) with that of alloHCT from matched sibling donors

(msdHCT), matched unrelated donors with in‐vivo T‐cell depletion

(mudHCT‐TCD), and matched unrelated donors without T‐cell

depletion (mudHCT‐TRD) in patients with peripheral T‐cell lym-

phoma (PTCL).

Methods: Eligible for this retrospective registry study were patients

aged 18 or older who had undergone alloHCT for anaplastic large cell

lymphoma(ALCL), angioimmunoblastic T‐cell lymphoma (AITL), or

PTCL‐not other speciﬁed (PTCL‐NOS) from the 4 donor types

described between 2008 and 2018 and were registered with the

CIBMTR or the EBMT. Co‐primary endpoints were overall survival

(OS) and progression‐free survival (PFS); secondary endpoints

included engraftment, acute and chronic GVHD, non‐relapse mor-

tality (NRM), and relapse/progression incidence (RI).

Results: Altogether 1942 patients were eligible (haploHCT 237;

msdHCT 911; mudHCT‐TCD 468; mudHCT‐TRD 326). HaploHCT

and matched aloHCT recipients were comparable for histology, age,

gender, comorbidity score, pretreatment lines, prior autoHCT, and

disease status at HCT. However, haploHCT patients were more likely

to have a Karnofsky score of 90‐100, and had more often received

reduced intensity conditioning as well as bone marrow grafts

(31% vs 6%).

On univariate and multivariate comparisons, OS and PFS, RI, and

NRM were not signiﬁcantly different between haploHCT, msdHCT,

mudHCT‐TCD, and mudHCT‐TRD with 3‐year estimates for OS and

PFS of 60%, 63%, 59%, and 64; and 50%, 50%, 48%, and 52%,

respectively. Engraftment was signiﬁcantly delayed after haploHCT

(neutrophils >0.5/nl at d +28 86% vs 95%, 94%, 97%, respectively, p

<0.001; platelets >20/nl at d +100 80% vs 96%, 93%, 96%,

respectively, p <0.001). Whilst risk of acute GVHD was comparable

between haploHCT, msdHCT, and mudHCT‐TCD, there was a lower

1‐year cumulative incidence of chronic GVHD after haploHCT (28%

vs 41%, 35%, and54%; p <0.001); retaining signiﬁcance after

multivariate adjustment for confounders. Factors signiﬁcantly

impairing both OS and PFS on multivariate analysis were advanced

disease status at alloHCT, age >50, and poor Karnofsky score. Pa-

tients undergoing alloHCT in 1

line had signiﬁcantly better OS than

patients allografted later.

Conclusions: These data, the largest study to date, conﬁrm that

alloHCT can result in durable PFS in a sizable proportion of patients

with ALCL, AITL, and PTCL‐NOS. The outcome of haploHCT in PTCL

is comparable to that of matched donor alloHCT, suggesting that

haploHCT might be a valid alternative in this setting.

Keywords: Stem Cell Transplant

Conﬂicts of interests pertinent to the abstract

P. Dreger

Consultant or advisory role: Gilead, Novartis, BMS, Bluebird Bio,

Takeda

054 |LACUTAMAB IN PATIENTS (PTS) WITH ADVANCED

MYCOSIS FUNGOIDES (MF) ACCORDING TO KIR3DL2

EXPRESSION: EARLY RESULTS FROM THE TELLOMAK PHASE 2

TRIAL

M. Bagot

, Y. Kim

, P. L. Zinzani

, S. Dalle

, M. Beylot‐barry

P. L Ortiz‐Romero

, A. Cambalia

, O. Dereure

, L. Mortier

E. Jacobsen

, F. Rotolo

, H. A Azim Jr

, P. Porcu

Hopital St Louis, Dermatology, Paris, France,

Stanford Cancer Center,

Dermatology, San Francisco, USA,

Policlinico S. Orsola‐Malpighi,

Oncology Hematology, Bologna, Italy,

Hospices Civils de Lyon,

Dermatology, Lyon, France,

Centre Hospitalier Universitaire de

Bordeaux ‐Hôpital Saint‐Andre, Dermatology, Bordeaux, France,

Hospital 12 de Octubre Medical School, Dermatology, Madrid, Spain,

Hospital Clínic de Barcelona, Dermatology, Barcelona, Spain,

CHU

Montpellier, Dermatology, Montpellier, France,

CHRU de Lille ‐Hôpital

Claude Huriez, Dermatology, Lille, France,

Dana‐Farber Cancer

Institute, Oncology Hematology, Boston, USA,

Innate Pharma, Clinical

Affaires, Marseille, France,

Innate Pharma, Clinical Development,

Marseille, France,

Thomas Jefferson University, Hematology Oncology,

Philadelphia, USA

SUPPLEMENT ABSTRACTS

Background: KIR3DL2 is a killer immunoglobulin‐like receptor,

expressed in >90% of Sézary Syndrome (SS) pts and 50% in pts with

MF. Lacutamab is a humanized ﬁrst‐in‐class monoclonal antibody

designed to deplete KIR3DL2‐expressing cells via antibody‐

dependent cell‐cytotoxicity and phagocytosis. In a previous phase 1

trial, lacutamab showed adequate safety proﬁle with no dose limiting

toxicities and a global response rate of 42.9% in pts with SS, with a

median time to response of 4.9 months (m).

Methods: TELLOMAK is an open‐label, multi‐cohort, international

phase II trial. Up to 148 pts are planned to be enrolled. Pts are

allocated to one of three cohorts: Cohort 1: SS, Cohort 2: KIR3DL2

expressing (≥1%) MF and Cohort 3: KIR3DL2 non‐expressing MF,

based on central KIR3DL2 testing. Eligible pts should have received

at least 2 prior systemic therapies with no evidence of large cell

transformation. Lacutamab 750 mg is administered as an intravenous

(i.v.) infusion weekly x 5 weeks (w), every 2 w x 10 then every 4 w,

until progression or unacceptable toxicity. The primary endpoint is

global conﬁrmed response, evaluated using the International

Consensus Criteria. Secondary endpoints include safety, quality of

life, other efﬁcacy endpoints, and biomarker analysis. Evaluable pts

should have at least one response assessment 5 w after treatment

initiation. In each of the MF cohorts, the study follows a Simon 2‐

stage design in which 21 and 18 pts were required in stage 1 for

Cohorts 2 and 3, respectively with early termination if <3 global

conﬁrmed responses per cohort were observed. Here we report early

stage 1 data for the two MF cohorts.

Results: As of January 20 2021, recruitment in stage 1 for both

cohorts 2 and 3 is ongoing, with 12 pts enrolled in each

cohort. Median age for all 24 pts is 57 years (range: 19‐81). At

study entry, 42% (n =5) and 17% (n =2) had stage III/IV in

cohorts 2 and 3, respectively. Median number of prior systemic

therapies is 3.5 (range: 2‐10). At a median follow‐up of 2.8 m

(range: 0.3‐14.1 m), 7 and 6 pts in cohort 2 and 3, respectively,

are ongoing treatment. Overall, 19 pts were evaluable for

response in Cohort 2 (n =11) and Cohort 3 (n =8). In Cohort 2,

5 skin responses were observed, of whom 3 had global conﬁrmed

responses (1 complete response, 2 partial responses). 7 pts had

global stable disease. No responses are reported yet in Cohort 3.

Adverse events (AEs) of any grade were observed in 17/24 pts

(71%), of which 10/24 (42%) were treatment‐related [TR]. Grade

≥3 AEs were observed in 2/24 (8%) pts, of which 1/24 (4%) was

TR. Most common AEs were asthenia (N =6, 25%; TR: 2),

pruritus (N =3, 12%; TR: 0), and peripheral oedema (N =2, 8%;

TR: 1).

Conclusion: Lacutamab met the predeﬁned threshold of activity in

the KIR3DL2 expressing MF cohort required to expand recruitment

to 50 pts. Safety proﬁle is reassuring and consistent with previous

phase 1 data. Updated results on all stage 1 pts from cohort 2 and 3

will be presented.

The research was funded by: Innate Pharma

Keywords: Cutaneous non‐Hodgkin lymphoma, Molecular Targeted

Therapies

Conﬂicts of interests pertinent to the abstract

M. Bagot

Consultant or advisory role: Innate Pharma, Kyowa Kirin, Takeda,

Galderma, Helsinn, recordati rare diseases

P. L Ortiz‐Romero

Consultant or advisory role: Kyowa Kirin, Takeda, 4SC, Helsinn,

Miragen, Innate Pharma, Recordati Rare diseases

F. Rotolo

Employment or leadership position: Innate Pharma

Stock ownership: Innate Pharma

H. A. Azim Jr

Employment or leadership position: Innate Pharma

Stock ownership: Innate Pharma

P. Porcu

Consultant or advisory role: Daiichi

Honoraria: Viracta, Innate Pharma, Kyowa Kirin, Verastem, Daiichi

Research funding: Viracta, Innate Pharma, Kyowa Kirin, Daiichi,

BeiGene, Incyte

Other remuneration: Scientiﬁc Boards: Viracta, Innate Pharma,

Kyowa Kirin, BeiGene

055 |MULTI‐CENTER PHASE II STUDY OF ROMIDEPSIN PLUS

LENALIDOMIDE FOR PATIENTS WITH PREVIOUSLY UNTREATED

PERIPHERAL T‐CELL LYMPHOMA (PTCL)

J. Ruan

, J. M Zain

, B. Palmer

, B. Borko Jovanovic

, X. Mi

A. Swaroop

, J. Winter

, L. I Gordon

, R. Karmali

, B. Pro

Weill Cornell Medicine, New York Presbyterian Hospital, Medicine,

Hematology‐Oncology, New York City, New York, USA ,

City of Hope

Comprehensive Cancer Center, Medicine, Duarte, USA,

Robert H. Lurie

Comprehensive Cancer Center, Northwestern University Feinberg School

of Medicine, Medicine, Chicago, USA,

Northwestern University Fein-

berg School of Medicine, Department of Preventive Medicine, Chicago,

USA,

Northwestern University Feinberg School of Medicine, Depart-

ment of Medicine, Chicago, USA

Introduction: PTCL are aggressive malignancies associated with poor

prognosis when treated with cytotoxic chemotherapy. Novel agents,

such as HDAC inhibitor romidepsin and immunomodulatory agent

lenalidomide, have shown clinical activities both as single agents and

when combined in R/R PTCL. We hypothesize that upfront treatment

with these agents is an effective and well‐tolerated option to defer

chemotherapy, particularly in patients who are not candidates for

intensive approach. We report the ﬁndings of the ﬁrst chemo‐free

combination of romidepsin plus lenalidomide as initial treatment

for PTCL (ClinicalTrials.gov‐NCT02232516).

Methods: Patients with previously untreated PTCL who were over

60 or noncandidates for chemotherapy based on comorbidity CIRS

score were eligible. Treatment was initiated with romidepsin 10

mg/m2 IV on d 1, 8, 15, and lenalidomide 25 mg PO on d 1‐21 of

SUPPLEMENT ABSTRACTS

28‐day cycle for up to 1 year, unless discontinued prior due to

POD, toxicities, or withdrawal of consent. The primary objective

was to evaluate ORR per Cheson criteria. Secondary objectives

included safety, PFS, OS, DOR, and delay to chemotherapy. The

sample size was 20 evaluable patients, which allows to estimate

the underlying true response rate with the margin of error of an

approximate 95% conﬁdence interval equal to 0.22, assuming the

true ORR =0.5.

Results: The study enrolled 29 subjects at 3 US centers, including

16 (55%) AITL, 11 (38%) PTCL‐NOS, 1 ATLL and 1 EATCL. The

median age was 75 (range 49‐84), and M:F ratio was 1:1. Nineteen

(66%) had stage III/IV disease, 23 (79%) had elevated LDH, and 9

(31%) had IPI 3‐5. Treatment was generally well tolerated

with expected side effects. Grade 3‐4 hematologic toxicities

included neutropenia (45%), thrombocytopenia (34%) and anemia

(28%). Grade 3‐4 non‐hematologic toxicities included hyponatremia

(45%), hypertension (38%), hypoalbuminemia (24%), fatigue (17%),

hyperglycemia (14%), hypokalemia (14%), dehydration (10%), lung

infection (10%) and sepsis (10%). At a median follow‐up of 8

months, 20 subjects were evaluable and received a median treat-

ment of 6 cycles. The ORR was 75% (95%CI: 50.9%, 91.3%) with

CR at 30% (11.9%, 54.3%). For AITL, the ORR was 84.6% (54.6%,

98.1%) with CR at 38.5% (13.9%, 68.4%). Median DOR was 4.2

months for all responders, and 14.3 months for CR patients.

The estimated 1‐yr PFS was 54.3% with 3‐yr PFS at 36.2%, and

the estimated 1‐yr OS was 76.0% with 3‐yr OS at 51.3%. Two

subjects moved onto consolidative ASCT in remission, and 4

received additional cytotoxic chemotherapy after progression.

Conclusions: This study provides the ﬁrst demonstration

that chemo‐free biologic combination of romidepsin and lenalido-

mide is feasible and effective as initial therapy for PTCL patients

who are not candidates for cytotoxic chemotherapy. These data

justify further evaluation of such novel agents as a frontline

strategy.

EA ‐previously submitted to ASCO 2021

The research was funded by: BMS / Celgene

Keywords: Molecular Targeted Therapies, Targeting the Tumor

Microenvironment

Conﬂicts of interests pertinent to the abstract

J. Ruan

Consultant or advisory role: BMS/Celgene, Seagen, Daiichi Sankyo

Honoraria: Kite Pharma

Research funding: BMS/Celgene, AstraZeneca, Pharmacyclics, Sea-

gen, Daiichi Sankyo

J. M. Zain

Consultant or advisory role: Verastem, Legend Biotech, Ono

Pharmaceutical

Honoraria: Seagen, Verastem, Kyowa Kirin

Research funding: Seagen, Crispr Therapeutics, Afﬁmed Therapeu-

tics, Onco Taris

J. Winter

Consultant or advisory role: Merck

Honoraria: Merck, Karyopharm Therapeutics

B. Pro

Consultant or advisory role: Corvus Pharmaceuticals

Honoraria: Takeda, Seagen, Portola Pharmaceuticals, Celgene, Bayer,

Kyowa Kirin

Research funding: Celgene, Takeda, Verastem

SUPPLEMENT ABSTRACTS

056 |THE COMBINATION OF DUVELISIB AND ROMIDEPSIN

(DR) IS HIGHLY ACTIVE AGAINST RELAPSED/REFRACTORY

PERIPHERAL T‐CELL LYMPHOMA WITH LOW RATES OF

TRANSAMINITIS: FINAL RESULTS

S. M. Horwitz

, A. J. Moskowitz

, N. Mehta‐Shah

, E. D. Jacobsen

M. S. Khodadoust

, N. Ganesan

, E. Drill

, H. Hancock

, T. Davey

P. Myskowski

, C. Maccaro

, W. Blouin

, J. Schwieterman

E. Cathcart

, S. Fang

, L. Perez

, S. Ryu

, N. Galasso

, D. Straus

D. C. Fisher

, A. Kumar

, A. Noy

, L. Falchi

, A. Dogan

, Y. H. Kim

D. Weinstock

Memorial Sloan Kettering Cancer Center, Medicine/Lymphoma, New

York, New York, USA,

Washington University, Medicine, Olivette, USA,

Dana Farber Cancer Institute, Medical Oncology/Hematologic Neoplasia,

Boston, USA,

Stanford University Medical Center, Medicine (Oncology)

and Dermatology, Stanford, USA,

Memorial Sloan Kettering Cancer

Center, Epidemiology‐Biostatistics, New York, USA,

Memorial Sloan

Kettering Cancer Center, Medicine/Dermatology, New York, USA,

Stan-

ford University School of Medicine and Stanford Cancer Institute, Medi-

cine (Oncology) and Dermatology, Stanford, USA,

Memorial Sloan

Kettering Cancer Center, Pathology, New York, USA

Introduction: Standard therapies for most relapsed/refractory (R/R)

T‐cell lymphomas (TCL) have overall response rates (ORR) of 25%‐

35%. Phosphoinositide‐3‐kinase (PI3K) δand γisoforms can promote

tumor cell autonomous and nonautonomous effects in TCL. Initial

studies of the PI3K‐δ/γinhibitor duvelisib (D) in R/R TCL showed an

ORR of 50% and CR of 19%, but also a 40% rate of grade (Gr) 3/4

ALT elevation at the MTD of 75 mg BID (Horwitz et al Blood 2018).

Based on preclinical data, we initiated a phase I study of D with either

romidepsin (R) or bortezomib. Based on efﬁcacy and safety, Arm A

(DR) was expanded to further describe safety and subtype‐speciﬁc

efﬁcacy.

Methods: 66 patients were treated on Arm A, with 59 at the MTD of

D 75mg BID +R 10 mg/m2 on days 1, 8, 15 of a 28 day cycle with

prophylaxis against VZV and PJP. Response was assessed q2 cycles x

3 then q3 cycles. 10 patients received 1 cycle (Lead In) of D 75 mg

BID alone prior to combination DR. Patients proceeding to transplant

were censored.

Results: 55 patients with PTCL and 11 with CTCL were treated

(Table 1). No DLTs were seen in the phase 1 on Arm A so dose level 3

(D 75 +R 10) was deemed the MTD.

At the MTD, 50/59 (85%) had AEs Gr 3‐4 (no Gr 5) possibly related

to study drug. AEs ≥Gr 3 in ≥10% of pt were: neutropenia (36%),

diarrhea (15%), increased ALT/AST (14%), thrombocytopenia (10%),

and infection (10%). 5 patients (9%) had ≥Gr 3 rash. 12 had any Gr

oropharyngeal/esophageal candidiasis; 2 Gr3. In 10 patients who

began on D‐only Lead In, 4 (40%) had ≥Gr 3 ALT/AST and 3/10 had

≥Gr 3 diarrhea. By contrast, only 4 /49 (8%) who got R +D in cycle 1

had Gr 3‐4 ALT/AST (p =.022) and 6/49 had ≥Gr 3 diarrhea (p =

.170).

64/66 patients were evaluable for response. ORR was 55% (35/64)

and CR was 34% (22/64). In PTCL, ORR was 58% (31/53) and CR

was 42% (22/53). In CTCL, ORR was 36% (4/11), all PR. Response

by histology is in Table 1. Of responders, 15/35 (43%) proceeded

to allo‐SCT with curative intent, after a median of 4 cycles. Me-

dian PFS was 6.9 m (PTCL) and 5.5 m (CTCL) and median DOR

was 8.1 m. 4 subjects had CR to single agent D on Lead‐in and did

not proceed to DR; 2/4 went to SCT and 1/4 remains on D at

42m.

Conclusion: DR is highly active in R/R PTCL. Adding Romidepsin to

Duvelisib 75 mg BID is safe and reduces Gr 3‐4 transaminitis

compared to Duvelisib at the same dose. The high rates of CR and

frequent bridging to allotransplant support the value of DR for pa-

tients with R/R PTCL.

The research was funded by Verastem/SecuraBio for this

clinical trial

Keywords: Aggressive T‐cell non‐Hodgkin lymphoma, Chemotherapy,

Combination Therapies

TABLE 1Response by Histology

100

SUPPLEMENT ABSTRACTS

Conﬂicts of interests pertinent to the abstract

S. M. Horwitz

Consultant or advisory role: Acrotech Biopharma, ADC Therapeutics,

Astex, C4 Therapeutics, Celgene, Janssen, Kura Oncology, Kyowa

Hakko Kirin, Myeloid Therapeutics, ONO Pharmaceuticals, Seattle

Genetics, Shoreline Bio, Takeda, Trillium Therapeutics, Tubulis,

Verastem, SecuraBio, and Vividion Therapeutics.

Honoraria: Takeda

Research funding: ADC Therapeutics, Afﬁmed, Aileron, Celgene,

Daiichi Sankyo, Forty Seven, Inc., Kyowa Hakko Kirin, Millennium/

Takeda, Seattle Genetics, Trillium Therapeutics, and Verastem/

SecuraBio

A. J. Moskowitz

Consultant or advisory role: Imbrium Therapeutics L.P, Janpix Ltd.,

Merck, Seattle Genetics, and Takeda

Research funding: ADC Therapeutics, Miragen, Seattle Genetics,

Merck, Bristol‐Myers Squibb, and Incyte

N. Mehta‐Shah

Consultant or advisory role: Kiowa Hakka Kirin, Karyopharm Ther-

apeutics, C4 Therapeutics, Daiichi Sankyo, Ono Pharmaceuticals,

SecuraBio

Research funding: Bristol Myers Squibb, Celgene, Verastem, Innate

Pharmaceuticals, Corvus Pharmaceuticals, Genentech/Roche

D. C. Fisher

Consultant or advisory role: Verastem

A. Kumar

Consultant or advisory role: Celgene, Kite Pharmaceuticals

Research funding: Abbvie Pharmaceuticals, Adaptive Bio-

technologies, Pharmacyclics, Seattle Genetics, Astra Zeneca –

Steering Committee for MCL Registry

A. Dogan

Consultant or advisory role: Corvus Pharmaceuticals, Physicians’

Education Resource, Seattle Genetics, Takeda, Roche, EUSAPharma,

PeerView

Research funding: Roche and Takeda

D. Weinstock

Consultant or advisory role: Secura Pharma

Research funding: Verastem

057 |EARLY SAFETY AND EFFICACY DATA FROM A PHASE I/II

TRIAL OF DZD4205, A SELECTIVE JAK1 INHIBITOR, IN

RELAPSED/REFRACTORY PERIPHERAL T‐CELL LYMPHOMA

W.‐S. Kim

, D.‐H. Yoon

, Y. Song

, Y. Koh

, J. Cao

, D. Ji

, H. Yang

H.‐S. Eom

, H. Jing

, J.‐Y. Kwak

, W.‐S. Lee

, J.‐S. Lee

, H.‐J. Shin

J. Jin

, M. Wang

, J. Li

, X. Huang

, X. Deng

, Z. Yang

, J. Zhu

Samsung Medical Center, Department of Hematology and Oncology,

Seoul, Korea,

Asan Medical Center, Department of Oncology ‐

Hematologic Cancer & BMT center, Seoul, Korea,

Peking University

Cancer Hospital, Department of Lymphoma, Beijing, China,

Seoul

National University Hospital, Department of Hemato‐Oncology Cen-

ter, Seoul, Korea,

Fudan University Shanghai Cancer Center, Depart-

ment of Oncology, Shanghai, China,

Zhejiang Cancer Hospital,

Department of Lymphoma, Hangzhou, China,

National Cancer Center,

Center for Hematologic Malignancy, Goyang, Korea,

Peking University

Third Hospital, Department of Hematology, Beijing, China,

Chonbuk

National University Hospital, Department of Hemato‐oncology, Jeonju,

Korea,

Inje University Busan Paik Hospital, Department of Hemato‐

oncology, Busan, Korea,

Seoul National University Bundang Hospital,

Department of Hematology & Medical Oncology, Seongnam, Korea,

Pusan National University Hospital, Department of Hemato‐oncology,

Busan, Korea,

The First Afﬁliated Hospital of Zhejiang University,

Department of Hematology, Hangzhou, China,

Dizal Pharmaceuticals,

Bioscience, Shanghai, China,

Dizal Pharmaceuticals, Clinical Devel-

opment, Shanghai, China,

Dizal Pharmaceuticals, Biostatistics,

Shanghai, China

Introduction: Relapsed or refractory (r/r) peripheral T cell lymphoma

(PTCL) is an aggressive lymphoma with poor prognosis. Most

approved therapies demonstrated overall response rates (ORR) <

30% and short progression free survival. DZD4205 (AZD4205), a

potent and highly selective JAK1 inhibitor, demonstrated profound

anti‐tumor activity in T lymphoma cells in vitro and tumor xenograft

in vivo, suggesting its potential as a therapeutic option for this unmet

medical need. In this abstract, we reported the preliminary data from

the ongoing phase I/II study of DZD4205 treating patients with r/r

PTCL (NCT04105010, JACKPOT8).

Methods: The JACKPOT8 study is an open label single arm study,

which aims to assess the safety, tolerability and anti‐tumor efﬁcacy

of DZD4205 in r/r PTCL. This study includes two parts. In Part A,

subjects with r/r PTCL who relapsed from or were refractory/

intolerant to systemic therapy were enrolled and dosed with

DZD4205 at 150 mg or 250 mg once daily. In Part B, subjects

received DZD4205 at a deﬁned dose. Safety and efﬁcacy were

assessed according to CTCAE version 5.0 and 2014 Lugano clas-

siﬁcation, respectively.

Results: As of December 7, 2020, a total of 47 subjects with r/r

PTCL were dosed with DZD4205 (150 mg, n =31; 250 mg, n =

16). Median age was 62.0 years (range: 29 ‐79), and median prior

systemic therapies were 2 lines (range: 1 ‐8). Six subjects had

undergone prior hematopoietic stem cell transplantation. Sixteen

subjects had bone marrow involvement at the baseline. Histologi-

cal subtypes included PTCL not otherwise speciﬁed (42.6%),

angioimmunoblastic T cell lymphoma (42.6%), ALK negative

anaplastic large cell lymphoma (6.4%), extra‐nodal nasal NK/T cell

lymphoma (6.4%) and monomorphic epitheliotropic intestinal T cell

lymphoma (2.1%).

Preliminary data showed that 41 subjects (87.2%) experienced

treatment emergent adverse events (TEAEs), among whom 24

(51.1%) had ≥grade 3 TEAEs. According to investigators, 16 subjects

SUPPLEMENT ABSTRACTS

101

(34.0%) had ≥grade 3 TEAEs possibly related to DZD4205. The most

common (>10%) ≥grade 3 TEAEs included thrombocytopenia

(23.4%), neutropenia (17.0%), and pneumonia (12.8%). Most TEAEs

were manageable and reversible with or without dose modiﬁcations.

As of December 7, 2020, 42 subjects (150 mg, n =27; 250 mg, n =

15) completed at least one post‐treatment tumor assessment. At 150

mg, 14 subjects showed tumor response, with ORR of 51.9%, among

whom 6 (22.2%) had complete response. At 250 mg, 6 subjects

showed tumor response, with ORR of 40.0%. Tumor response was

observed in various subtypes. The median duration of response (DoR)

was not reached, and the longest DoR was >12 months. Patient

enrolment is ongoing.

Conclusion: Early results from this ongoing phase I/II study suggest

good tolerability and promising anti‐tumor efﬁcacy of DZD4205 in r/

r PTCL, indicating its potential as a therapeutic option for this unmet

medical need.

The research was funded by: The research was funded by Dizal

(Jiangsu) Pharmaceutical Co., Ltd.

Ongoing Trial

Keywords: Molecular Targeted Therapies, Aggressive T‐cell non‐

Hodgkin lymphoma, Molecular Targeted Therapies

No conﬂicts of interests pertinent to the abstract.

SESSION 9: MANTLE CELL LYMPHOMA

058 |A SIMPLE EPIGENETIC SIGNATURE DEFINES

TWO BIOLOGIC GROUPS OF MANTLE CELL LYMPHOMA

M. M. Bühler

, M. Kulis

, M. Duran‐Ferrer

, G. Clot

, F. Nadeu

, A.

Navarro

, C. López

, E. Giné

, S. Beà

, E. Campo

, J. I. Martín‐Subero

Hospital Clínic Barcelona, IDIBAPS, Barcelona, Spain

Background: Mantle cell lymphoma (MCL) is a mature B cell

lymphoma with a generally poor prognosis. However, in the past

decade a subset of MCL with more indolent clinical course and

predominant leukemic disease, termed leukemic non‐nodal MCL

(nnMCL), has been identiﬁed. In order to tailor treatment taking

into account the different natural course of these diseases, it is

important to conﬁdently diagnose the two MCL subtypes. Current

strategies in the differential diagnosis between nnMCL and con-

ventional MCL (cMCL) include SOX11 expression and a gene

expression signature (L‐MCL16), but both methods present limi-

tations which pose difﬁculties in clinical practice. The epigenetic

characterization of MCL (Queirós AC et al., Cancer Cell 2016 and

Nadeu F et al., Blood 2020) identiﬁed two disease subtypes (C1

and C2), which mostly represent cMCL and nnMCL respectively.

Furthermore, a SOX11 distal enhancer region was discovered,

which is de novo demethylated in SOX11 positive MCL. Our study

aims to translate the epigenetic subtypes of MCL into a simple

assay, which can be easily implemented in clinical practice and

universally applied to all types of clinical samples. Furthermore we

will analyze the impact of the epigenetic disease subtype on clin-

ical outcome and we will characterize the methylation proﬁle of

regulatory regions of SOX11.

Methods: We identiﬁed a 3 CpG signature (Duran‐Ferrer M et al.,

Nature Cancer 2020) that accurately subclassiﬁes MCL into C1

(cMCL) and C2 (nnMCL) MCL. To overcome limitations of previous

methodologies, we designed pyrosequencing assays that can be

applied to any type of clinical sample, including frozen and

formalin‐ﬁxed parafﬁn‐embedded (FFPE) tissues, as well as pe-

ripheral blood samples. Extracted DNA was bisulﬁte converted,

ampliﬁed by PCR and pyrosequenced for quantitative methylation

analysis.

Results: Benchmarking experiments show an excellent technical

reproducibility and high correlation between different sample types

of the same patient. The exploratory study with 71 samples shows a

102

SUPPLEMENT ABSTRACTS

clear separation in two groups, which correspond to C1 and C2 MCL

(Figure). C1 MCL show SOX11 positivity by immunohistochemistry,

except for one single cases of pleomorphic MCL. All SOX11

expressing MCL show a consistent demethylation in the SOX11

regulatory regions, whereas a majority of SOX11 negative cases have

high methylation levels.

Conclusion: Our study highlights the stability and applicability of a

methylation signature to classify MCL subtypes. Analysis of the

methylation signature in an extended series of cases is currently

ongoing and will allow us to determine the prognostic signiﬁcance of

the epigenetic subtype of MCL. This epigenetic signature applicable

to any type of clinical samples may represent a novel and accurate

tool for the differential diagnosis of cMCL and nnMCL in clinical

routine.

EA ‐previously submitted to EHA 2021.

The research was funded by: the Ministerio de Ciencia e Innovación

(MCI), grant RTI2018‐094274‐B‐I00 and the NIH, grant

P01CA229100 (to E.C.). M.B. is supported by the Swiss Cancer

League (BIL KLS‐5130‐08‐2020) and the Nuovo‐Soldati Foundation

for Cancer Research.

Keywords: Genomics, Epigenomics, and Other ‐Omics, Aggressive B‐

cell non‐Hodgkin lymphoma, Pathology and Classiﬁcation of

Lymphomas

No conﬂicts of interests pertinent to the abstract.

059 |A COMPLETELY GENETIC PROGNOSTIC MODEL

OVERCOMES CLINICAL PROGNOSTICATORS IN MANTLE CELL

LYMPHOMA: RESULTS FROM THE MCL0208 TRIAL FROM THE

FONDAZIONE ITALIANA LINFOMI (FIL)

S. Ferrero

, R. Moia

, L. Cascione

, G. M. Zaccaria

, A. Rinaldi

B. Alessandria

, D. Grimaldi

, C. Favini

, A. Evangelista

, M. Schipani

F. Narni

, C. Stelitano

, P. M. Stefani

, F. Benedetti

, M. Mian

I. Casaroli

, M. Zanni

, C. Castellino

, V. Pavone

, S. Galimberti

F. Re

, D. Rossi

, S. Cortelazzo

, G. Gaidano

, M. Ladetto

F. Bertoni

Hematology, Department of Molecular Biotechnologies and Health

Sciences, University of Torino, Hematology 1, AOU “Città della salute e

della scienza di Torino”, Torino, Italy,

Division of Hematology,

Department of Translational Medicine, Università del Piemonte Orientale,

Novara, Italy,

Institute of Oncology Research, Faculty of Biomedical

Sciences, USI, Bellinzona, SIB Swiss Institute of Bioinformatics, Lausanne,

Switzerland,

Hematology and Cell Therapy Unit, IRCCS Istituto Tumori

'Giovanni Paolo II', Bari, Italy,

Institute of Oncology Research, Faculty of

Biomedical Sciences, USI, Bellinzona, Switzerland,

Hematology,

Department of Molecular Biotechnologies and Health Sciences, University

of Torino, Torino, Italy,

Unit of Cancer Epidemiology, CPO Piemonte, A.O.

U. Città della Salute e della Scienza di Torino, Torino, Italy,

Department

of Medical and Surgical Sciences, Section of Hematology, University of

Modena and Reggio Emilia, Azienda Ospedaliero Universitaria Policlinico,

Modena, Italy,

Hematology Department, AO “Bianchi‐Melacrino‐Morelli”,

Reggio Calabria, Italy,

Hematology Unit, General Hospital Ca' Foncello,

Treviso, Italy,

Hematology University Division, Verona Hospital, Verona,

Italy,

Department of Haematology and CBMT, Bolzano Hospital,

Bolzano, Italy,

Haematology Unit, ASST Monza San Gerardo, Monza,

Italy,

Hematology Unit, Azienda Ospedaliera SS Antonio e Biagio e

Cesare Arrigo, Alessandria, Italy,

Department of Hematology, S. Croce e

Carle Hospital, Cuneo, Italy,

UOC Ematologia e Trapianto, Az. Osp. C.

Panico, Tricase, Italy,

Section of Hematology, Department of Clinical

and Experimental Medicine, University of Pisa, Pisa, Italy,

Haematology

and Bone Marrow Transplant Unit, Parma General Hospital, Parma, Italy,

Institute of Oncology Research, Faculty of Biomedical Sciences, USI,

Bellinzona, Switzerland, Oncology Institute of Southern Switzerland (IOSI),

Bellinzona, Bellinzona, Switzerland,

Oncology Unit, Italy Medical &

Center Hospital Humanitas Gavazzeni and Castelli, Bergamo, Italy,

Division of Hematology, Department of Translational Medicine,

Università del Piemonte Orientale, Novara, Division of Hematology,

FIGURE 1

SUPPLEMENT ABSTRACTS

103

Azienda Ospedaliera SS Antonio e Biagio e Cesare Arrigo, Alessandria,

Italy

Introduction: TP53 and KMT2D disruptions, as well as high risk MIPI‐

c were independent prognosticators for younger mantle cell lym-

phoma (MCL) patients enrolled in the FIL MCL0208 trial

(NCT02354313, upfront high dose immune‐chemotherapy and

autologous transplantation, ASCT, followed by randomized lenalido-

mide maintenance) and were thus integrated in the MIPI‐g prog-

nostic model [Ferrero, 2020]. Furthermore, MCL is characterized by

many copy number variations (CNVs), whose clinical impact is not

clearly understood. This study aimed at reﬁning the MIPI‐g model by

incorporating CNVs.

Methods: DNA from bone marrow CD19+sorted cells was pro-

ﬁled with the Illumina HumanOmni2.5 array in 165 patients.

Minimal common regions were identiﬁed by bioinformatic pipeline

and smaller regions with GISTIC algorithm: both were considered

as CNVs. Progression free survival (PFS) was the primary endpoint.

Results: 351 CNVs were identiﬁed in at least one patient. Besides

TP53 deletion (already included in MIPI‐g) 10 further CNVs

showed predictive by univariate analysis and were selected for

multivariate Cox modelling (multiple comparisons were corrected

by Bonferroni). Actually, 4 CNVs maintained independent associa-

tion with PFS: Loss@chr22 in 10/165 (6%) patients with a HR of

4.14 (p =0.028), LOH@chr17 in 5 (3%) with a HR of 4.79 (p =

0.010), HDEL@chr9 in 3 (2%) with a HR of 18.1 (p =0.001) and

CDKN2A loss in 30 (18%) with a HR of 2.6 (p =0.002). Patients

with at least one of these 4 CNVs had 3y PFS of 34% compared

to 80% for wild type (WT) (p <0.001) and 3y overall survival (OS)

of 66% compared to 93% for WT (p <0.001). By using the same

approach employed for the MIPI‐g, we assigned a score to each

single predictor based on the Cox regression analysis. KMT2D

mutations (HR 2.43, 95% CI 1.21‐4.87, p =0.012) TP53

disruptions (HR 2.63, 95% CI 1.38‐5.02, p =0.003) and 4CNVs

(HR 2.56, 95% CI 1.43‐4.61, p =0.002) had superimposable HRs

for PFS and thus scored 1 point. Interestingly, MIPI‐c high risk

class lost its independent prognostic value (HR 1.42, 95% CI 0.65‐

3.12, p =0.382), thus scoring 0 points. Consequently, a novel

“genetics‐only” model was developed, with patients grouped into 3

risk classes: i) 0 points, low risk group (LR =97, 60%); ii) 1 point,

intermediate risk (IR =41, 26%); iii) >2 points, high risk (HR =22,

14%). 3y PFS for LR, IR and HR was 86%, 50% and 24%,

respectively (p <0.0001, Fig 1A). The novel genetic score

improved the model discrimination ability, with a C‐statistics of

0.715 as compared to 0.675 for MIPI‐g. Interestingly, this model

was highly promising in terms of OS, too: actually, 3y OS for LR,

IR and HR was 92%, 74% and 59%, respectively (Fig 1B).

Discussion: The inclusion of 4CNVs into the MIPI‐g allowed the

development of a completely molecular model that improved the

stratiﬁcation in MCL, enriching the HR group of patients, primary

refractory or destined to an early relapse after high dose chemo-

therapy and ASCT.

Keywords: Risk Models, Diagnostic and Prognostic Biomarkers,

Aggressive B‐cell non‐Hodgkin lymphoma

No conﬂicts of interests pertinent to the abstract.

060 |EFFICACY AND SAFETY OF IBRUTINIB IN COMBINATION

WITH RITUXIMAB AS FRONTLINE TREATMENT FOR INDOLENT

CLINICAL FORMS OF MANTLE CELL LYMPHOMA. RESULTS OF

THE GELTAMO IMCL‐2015 STUDY

E. Giné

, F. De la Cruz

, A. Jiménez Ubieto

, J. López Jiménez

A. Martín García‐Sancho

, M. J. Terol

, E. González‐Barca

M. Casanova

, A. De la Fuente Burguera

, A. Marín Niebla

FIGURE 1 PFS (A) and OS (B) according to the novel genetics‐only score

104

SUPPLEMENT ABSTRACTS

A. Muntanola Prat

, T. J. González‐López

, M. Aymerich

X. Setoain

, M. Cortés‐Romera

, A. Rotger

A. Medina

R. García‐Sanz

, E. Campo

, A. López‐Guillermo

Hospital Clínic of Barcelona, IDIBAPS, CIBERONC, Hematology,

Barcelona, Spain,

Hospital Universitario Virgen del Rocio, Hematology,

Sevilla, Spain,

Hospital Universitario 12 de Octubre, Hematology,

Madrid, Spain,

Hospital Universitario Ramón y Cajal, Hematology,

Madrid, Spain,

Hospital Clínico Universitario Salamanca, IBSAL,

CIBERONC, Hematology, Salamanca, Spain,

Hospital Universitario

Clínic de Valencia, INCLIVA, Hematology, Valencia, Spain,

Hospital

Duran i Reynals, ICO, IDIBELL, Hematology, Hospitalet de Llobregat,

Spain,

Hospital Costa del Sol, Hematology, Marbella, Spain,

Anderson Cancer Center, Hematology, Madrid, Spain,

Hospital

Universitari Vall d'Hebrón, Hematology, Barcelona, Spain,

Hospital

Mútua de Terrassa, Hematology, Terrassa, Spain,

Hospital

Universitario de Burgos, Hematology, Burgos, Spain,

Hospital Clínic of

Barcelona, Hematopathology Unit, Barcelona, Spain,

Hospital Clínic of

Barcelona, Nuclear Medicine, Barcelona, Spain,

Hospital Universitari

de Bellvitge, Nuclear Medicine, Hospitalet de Llobregat, Spain,

Hospital General Universitario Gregorio Marañón, Nuclear Medicine,

Madrid, Spain,

Hospital Clínic of Barcelona, IDIBAPS, CIBERONC,

Universitat de Barcelona, Hematopathology Unit, Barcelona, Spain,

Hospital Clínic of Barcelona, IDIBAPS, CIBERONC, Universitat de

Barcelona, Hematology, Barcelona, Spain

SUPPLEMENT ABSTRACTS

105

Introduction: Mantle‐cell lymphoma (MCL) is a heterogeneous dis-

ease and the existence of indolent clinical forms is increasingly

recognized. The aim of this study was to propose a frontline tailored

treatment for indolent clinical forms with ibrutinib in combination

with rituximab (IR).

Methods: This is a multicenter single‐arm, open‐label, phase II

study with a two‐stage design conducted in 14 Spanish GELTAMO

sites (NCT02682641). Centralized histology, PET‐CT review,

minimal residual disease (MRD) studies (qPCR and NGS in pe-

ripheral blood [PB] and bone marrow [BM]) and biological studies

are conducted. Previously untreated MCL patients with indolent

clinical forms were eligible according to the following criteria: no

symptoms attributable to MCL, ECOG 0‐1, stable disease without

therapy need for at least 3 months, non‐blastoid variants, Ki‐67

<30% and largest tumor diameter ≤3 cm. Both leukemic non‐

nodal and nodal forms were acceptable. Patients received

ibrutinib 560 mg daily and a total of 8 doses of rituximab 375

mg/m2 (4 weekly doses during the ﬁrst 28‐day cycle, followed

by day 1 of cycles 3, 5, 7 and 9). Ibrutinib could be discontinued

after 2 years of treatment in case of sustained undetectable

MRD. The primary endpoint was the rate of complete re-

missions (CR) achieved after 12 cycles according to the Lugano

criteria.

Results: Fifty patients (Male 66%; median age 65 years) were

enrolled in the study (June 2016 to December 2019, data cut‐off 22

Jan 2021, median follow‐up 33 months). Efﬁcacy data of the 50 pa-

tients included four cases that were discontinued earlier due to

adverse events (AE): ORR 84% and CR 80%. Regarding MRD evalu-

able cases (N =45), 86% achieved undetectable MRD in PB and 64%

also in BM. In CR cases, 72% had undetectable MRD in both PB and

BM.

After 24 months of treatment, 19 patients were in response with

undetectable MRD and discontinued ibrutinib treatment according

to protocol. Four patients progressed from the disease at 12, 38,

40 and 52 months of follow‐up and two of them eventually died of

progression. Overall, PFS and OS estimated at 42 months were

81% (95% CI: 65‐98) and 86% (95% CI: 71‐100), respectively. Five

patients were withdrawn from the study due to serious adverse

events (one each), including skin rash, severe aplastic anemia,

pancreatic adenocarcinoma, and lumbar fractures, or by decision of

the patient. The most common treatment‐related adverse events

(AE) were diarrhea (38%), neutropenia (36%), fatigue (32%), upper

respiratory infection (26%) nausea (22%), and arterial hypertension

(20%). AE grades ≥3‐4 corresponded predominantly to hemato-

logic toxicity (22%). So far 10/50 patients have discontinued

ibrutinib due to intolerance.

Conclusion: In indolent clinical forms of MCL frontline ibrutinib in

combination with rituximab has a high efﬁcacy, including unde-

tectable MRD in the majority of cases, with a predictable toxicity

proﬁle.

The research was funded by: Janssen Clinical Investigator‐Initiated

Study (IIS) Research Support

Keywords: Aggressive B‐cell non‐Hodgkin lymphoma, Molecular

Targeted Therapies

Conﬂicts of interests pertinent to the abstract

E. Giné

Consultant or advisory role: Gilead

Honoraria: Janssen, Gilead, Roche, Genmab

Research funding: Janssen, Gilead, Roche

Educational grants: Janssen, Gilead

061 |THE COMBINATION OF VENETOCLAX, LENALIDOMIDE

AND RITUXIMAB IN PATIENTS WITH NEWLY DIAGNOSED

MANTLE CELL LYMPHOMA INDUCES HIGH RESPONSE RATES

AND MRD UNDETECTABILITY

T. J. Phillips

, D. Bond

, S. Devata

, A. Danilov

, A. Herrera

K. Maddocks

, R. Wilcox

, Y. Karimi

, S. Carty

, M. Kaminski

L. Popplewell

University of Michigan, Hematology‐Oncology, Ann Arbor, USA,

Ohio

State University, Hematology/Oncology, Columbus, USA,

Medical College

of Wisconsin, Hematology/Oncology, Milwaukee, USA,

City of Hope,

Hematology/Oncology, Duarte, USA

Background: MCL is a rare lymphoma without a standard of care but

several regimens have demonstrated clinical activity, the majority

based on traditional chemotherapy. We hypothesized that adding

venetoclax (V) to R2 would be safe and effective in MCL pts irre-

spective of age, morphology or stage. Here we present safety and

efﬁcacy data from the on‐going phase 1b study of R2 +V in pts with

newly diagnosed MCL.

Methods: This multi‐center phase 1 study (NCT03523975)

enrolled pts aged ≥18 yrs with untreated MCL. The primary

objective was to characterize the safety and tolerability of R2 +V

and determine the MTD. During induction (12 months (m)) pts

received lenalidomide (L) 20 mg daily on day 1‐21, Rituximab (R)

was given weekly during c1 then on day 1 of every even cycle, V

was escalated over 4 weeks to 400 mg beginning day 8. Each cycle

is 28 days (d). The DLT period was 42 d beginning C1D8. In

maintenance, R every 8 weeks for 36m, L at 10 mg or half of last

dose during induction for 24 m and V for minimum 12 m. No pts

have been transplanted. Pts with progression (PD) came off study.

MRD was analyzed in parallel with scans during induction by

clonoSEQ assay (Adaptive Biotechnologies).

Results: As of Feb. 1st, 2021, we have enrolled all 28 planned pts

on study. Pt characteristics/responses are summarized in Table 1.

Among the 28 pts who have received at least one dose, the

106

SUPPLEMENT ABSTRACTS

median treatment duration so far is 278d (IQR 170‐560), with

24 pts still on treatment (Tx). 1 pt is off from a unrelated

condition.

All pts escalated to V 400 mg w/o any DLTs noted. Treatment‐

emergent adverse events (TEAEs) were reported in 100% of pts,

and grade 3+TEAEs were reported in 26 (93%) patients. The most

common all‐grade TEAEs (≥50% of pts), regardless of relationship to

study Tx, were fatigue, neutropenia and diarrhea. Grade ≥3 TEAEs

reported in ≥50% pts were neutropenia (68%) and thrombocytopenia

(50%). No pts have withdrawn or d/c Tx due to AEs. There was one

grade 5 event, in a non‐evaluable pt, related to a PE that occurred

prior to DLT period.

In the 28 evaluable pts the ORR (CR/PR) was 96% (27/28 pts) with

CR/CRu of 89%. Of the responding pts, two had PD, one w/ CR and

one w/ PR. All pts with PD had baseline TP53 mutation. MRD testing

was successful in all pts. At time of submission 20 of 28 (71%) were

MRD ‐at 10

‐6

Conclusions: Interim results show that at the MTD the combina-

tion of V 400 mg daily, L 20 mg, with R is safe with a manageable

toxicity proﬁle and a high ORR and MRD ‐in pts with

newly diagnosed MCL. Safety data is consistent with the AE proﬁle

noted for each drug without any unexpected or unique AEs.

Updated results including BH3 proﬁling will be presented at the

meeting.

EA ‐previously submitted to ASCO 2021

The research was funded by: Abbvie,Rogel Cancer Center, BMS (drug

only)

Keywords: Aggressive B‐cell non‐Hodgkin lymphoma, Combination

Therapies, Ongoing Trials

Conﬂicts of interests pertinent to the abstract

T. J. Phillips

Consultant or advisory role: Abbvie, BMS, Genentech, TG thera-

peutics, Gilead, Bayer, Incyte, ADCT therapeutics,

Research funding: AbbVie, Bayer, BMS

062 |SAKK 36/13 ‐IBRUTINIB PLUS BORTEZOMIB AND

IBRUTINIB MAINTENANCE FOR RELAPSED AND REFRACTORY

MANTLE CELL LYMPHOMA: FINAL REPORT OF A PHASE I/II

TRIAL OF THE EUROPEAN MCL NETWORK

U. Novak

, M. Fehr

, S. Schär

, M. Dreyling

, G. Scheubeck

S. Ramadan

, E. Zucca

, T. Zander

, G. Hess

, U. Mey

, S. Ferrero

N. Mach

, C. Boccomini

, S. Böttcher

, M. Voegeli

, A. Cairoli

T. Menter

, S. Dirnhofer

, S. Gadient

, K. Eckhardt

, C. Driessen

C. Renner

Inselspital, Bern University Hospital, Medical Oncology, Bern,

Switzerland,

Kantonsspital St. Gallen, Department of Medical Oncology

and Hematology, St. Gallen, Switzerland,

SAKK, Coordinating Center,

Bern, Switzerland,

Universität München‐Grossadern, Medizinische Klinik

III, München, Germany,

IEO, European Institute of Oncology IRCCS,

Onco‐Hematology Division, Milano, Italy,

Oncology Institute of Southern

Switzerland, Ospedale San Giovanni, Bellinzona, Switzerland,

Kant-

onsspital Luzern, Department Oncology, Luzern, Switzerland,

Johannes

Gutenberg Universität Mainz, Universitätsmedizin, Mainz, Germany,

Kantonsspital Graubünden, Department of Oncology and Hematology,

Chur, Switzerland,

AOU “Città della Salute e della Scienza di Torino”,

Hematology 1, Torino, Italy,

University Hospital of Geneva, Department

of Oncology, Genève, Switzerland,

Rostock University Medical Center,

Department of Medicine, Clinic III ‐Hematology, Oncology, Palliative

Medicine, Rostock, Germany,

Kantonsspital Baselland, Oncology, Liestal,

Switzerland,

CHUV University Hospital and University of Lausanne,

Service et Laboratoire Central d'Hématologie, Département d'Oncologie,

Lausanne, Switzerland,

University Hospital Basel, Institute of Pathology

and Medical Genetics, Basel, Switzerland,

Onkozentrum, Hirslanden &

Zürich, Zürich, Switzerland

Introduction: Mantle‐cell lymphoma (MCL) remains incurable with

frequent relapses, limited treatment options and progressively

shorter disease‐free survival with every relapse. The Bruton's

tyrosine kinase inhibitor ibrutinib (IBR) and the proteasome in-

hibitor bortezomib (BOR) have single agent activity and regulatory

approval in MCL. IBR and BOR lead to a downregulation of NF‐κB

activity via different targets. IBR resistance involves mutations in

genes of the NF‐κB pathway. In vitro, the combination of both

drugs provides synergistic cytotoxicity in BOR‐sensitive and re-

fractory MCL.

Methods: In this investigator‐initiated trial, we included patients

(pts.) with histologically conﬁrmed MCL, refractory/relapsed after ≤2

lines of a non‐BOR‐containing chemotherapy (incl. high‐dose

chemotherapy), and excluded pts. with prior BOR or IBR therapy,

with CNS disease, in need of anticoagulation, or active Hepatitis B, C

or HIV infection. Pts. received 6 21‐days cycles of IBR +BOR, fol-

lowed by IBR until progression or unacceptable toxicity. The dose of

the combination was established with 9 pts. in the phase I part: BOR

s.c. 1.3 mg/m

, days 1, 4, 8, 11 q3w, and IBR continuously at 560 mg/

day. The primary endpoint of the phase II was the overall response

rate (ORR) based on CT/MRI (Cheson, 1999). The null hypothesis was

TABLE 1

Sex, male, % (n) 64% (18)

Age, years, median (IQR) 65 (57, 69)

Race, white, % (n) 100% (28)

Tx duration, d, median (IQR) 278 (170, 560)

Stage IV, % (n) 96% (27)

MIPI High, % (n) 64% (18)

Blast/Pleo, % (n) 21% (6)

Ki‐67 ≥30%, % (n) 68% (19)

ORR 96%

CR/CRu 89%

MRD ‐71%

SUPPLEMENT ABSTRACTS

107

an OR ≤65%. Data on secondary endpoints were collected until

January 18, 2021.

Results: Since August 2015, 58 pts. received IBR+BOR (9 in

phase I (4 Swiss sites), and 49 in 11 additional sites in

Switzerland, Germany and Italy). The median age was 71 (47‐90),

78% were male. The ORR in 55 pts. (including those that received

560 mg IBR in phase I) to the combination was 81.8% (90% CI

71.1, 89.8%, CR(u) 21.9%). With continued IBR (median 6 months

(M)), the ORR increased to 87.3% (90% CI 77.4, 93.9%, CR(u)

43.7%). 31/55 pts. (56.4%) had at least one high‐risk feature. In

these, IBR+BOR was also effective (ORR 79% (90% CI 62, 90%),

n=28) for Ki‐67 >30%, ORR 73% (90% CI 44, 92), n =11) for

p53 overexpression by immunohistochemistry (>50%, suggestive

for mutations), and 67% (90% CI 34, 90%), n =9) for the blas-

toid/pleomorphic variants), and not different in terms of time to

best response from pts. with low risk features. With a me-

dian follow‐up of 24.4M, the median duration of response was

22.7M (95% CI 12.3, NA), and the median PFS was 18.6M

(95% 12.4, NA). All pts. had at least one adverse event (AE),

which was grade (G)3 in 67.3%, and G4 in 21.8%. G3 infections

(25%) and G4 hematotoxicity (16.4%) were the most frequent AEs

during the combination. Neurotoxicity, mostly G1&2 occurred in

14.5%.

Conclusions: The combination of Ibrutinib and Bortezomib shows

signiﬁcant and durable efﬁcacy in relapsed mantle‐cell lymphoma,

importantly also in patients with high‐risk features. In this setting,

this regimen is a rational comparator regimen for a future phase III

trial.

(ClinicalTrials.gov Identiﬁer: NCT02356458)

The research was funded by: Janssen‐Cilag

Keywords: Combination Therapies

Conﬂicts of interests pertinent to the abstract

U. Novak

Consultant or advisory role: Janssen‐Cilag, Celgene (BMS), Takeda,

Astra Zeneca, Roche, Novartis, Gilead, Pierre Fabre

Honoraria: Celgene (BMS), Novartis

M. Dreyling

Consultant or advisory role: Astra Zeneca, Bayer, Beigene, Celgene,

Gilead, Janssen, Novartis, Roche

Honoraria: Bayer, Celgene, Gilead, Janssen, Roche

Research funding: Abbvie, Bayer, Celgene, Janssen, Roche

U. Mey

Consultant or advisory role: Janssen‐Cilag

S. Ferrero

Consultant or advisory role: Janssen

Honoraria: Janssen

Research funding: Janssen

S. Böttcher

Honoraria: Roche, AbbVie, Janssen, Astra‐Zeneca, Sanoﬁ

Research funding: Janssen‐Cilag Neuss, Becton Dickinson

Heidelberg

C. Renner

Consultant or advisory role: Janssen‐Cilag

Honoraria: Janssen‐Cilag

063 |INDUCTION R

FOLLOWED BY MAINTENANCE IN

PATIENTS WITH RELAPSED/REFRACTORY MANTLE CELL

LYMPHOMA: INTERIM ANALYSIS FROM THE PHASE 3B

MAGNIFY STUDY

J. P. Sharman

, J. M. Melear

, A. Yacoub

, S. R. Fanning

D. J. Andorsky

, G. S. Nowakowski

, M. J. Rummel

, F. Lansigan

J. Li

, J. R. Ahn

, M. Gharibo

, M. Coleman

Willamette Valley Cancer Institute and Research Center, US Oncology

Research, Eugene, Oregon, USA,

Texas Oncology‐Austin, US Oncology

Research, Austin, USA,

University of Kansas Cancer Center, Depart-

ment of Hematology‐Oncology, Westwood, USA,

Prisma Health, US

Oncology Research, Greenville, USA,

Rocky Mountain Cancer Centers,

US Oncology Research, Boulder, USA,

Mayo Clinic, Division of He-

matology, Rochester, USA,

Justus‐Liebig Universität, Med. Clinic IV,

Hematology, Giessen, Germany,

Dartmouth‐Hitchcock Medical Center,

Division of Hematology and Oncology, Lebanon, USA,

Bristol Myers

Squibb, Global Biometrics and Data Sciences, Princeton, New Jersey,

USA,

Bristol Myers Squibb, US Medical Affairs Hematology, Princeton,

New Jersey, USA,

Clinical Research Alliance Inc, Weill Cornell Med-

icine, New York, USA

Background: The combination of lenalidomide +rituximab (R

) has

shown complementary clinical activity and is a tolerable regimen in

both untreated and relapsed or refractory (R/R) indolent non‐

Hodgkin lymphoma (NHL), as well as mantle cell lymphoma (MCL),

an uncommon but aggressive form of NHL.

Methods: MAGNIFY is a multicenter, phase 3b trial (NCT01996865)

in patients with R/R follicular lymphoma (FL) grades 1—3b, trans-

formed FL, marginal zone lymphoma, and MCL. Lenalidomide 20 mg

on d 1—21 of a 28‐d cycle +rituximab 375 mg/m

/wk cycle 1 and

then every 8 wk starting with cycle 3 (R

) is given for 12 cycles

followed by 1:1 randomization in patients with stable disease, partial

response, or complete response/complete response unconﬁrmed

(CR/CRu) to R

vs rituximab maintenance for 18 mo. The primary end

point is progression‐free survival (PFS) by 1999 International

Working Group (IWG) criteria. Secondary end points include safety,

CR rate, duration of response (DOR), duration of CR (DOCR), time‐

to‐response (TTR), time‐to‐next antilymphoma therapy, and overall

survival. This analysis evaluates the interim primary endpoint of

overall response rate (ORR) by 1999 IWG criteria and safety of R

108

SUPPLEMENT ABSTRACTS

induction in patients with MCL in the induction intention‐to‐treat

population.

Results: As of August 28, 2020, 73 patients with MCL were

enrolled (median age, 70.0 y [range, 51‐88]); 89% had stage III/IV

disease, and 41% had bulky disease (>7 cm or >3 cm �3 lymph

nodes). All patients had received prior rituximab‐containing ther-

apy, with 25 (34%) rituximab refractory (progression ≤6 mo after

last rituximab dose). Seven patients (10%) had received prior

ibrutinib. Median follow‐up was 31.7 mo for patients still alive.

ORR was 51%, with 34% CR rate (CR +CRu), irrespective of prior

refractory status to rituximab (Table). Median DOR was 31.6 mo;

median DOCR was not reached; median TTR was 2.8 mo, and

median PFS was 28.0 mo, with 1‐year PFS rate of 57%. The most

common treatment emergent adverse events (TEAEs) of any grade

were neutropenia (51%), fatigue (44%), diarrhea (32%), con-

stipation (28%), cough (28%), dyspnea (26%), and nausea (26%).

Grade 3/4 neutropenia was 46%; all other grade 3/4 TEAEs were

≤11%.

Conclusions: R

is an active and tolerated regimen with durable re-

sponses among patients with R/R MCL and mostly naive to Bruton

tyrosine kinase inhibitor therapy.

Keywords: Aggressive B‐cell non‐Hodgkin lymphoma

Conﬂicts of interests pertinent to the abstract

J. P. Sharman

Consultant or advisory role: Abbvie; Acerta Pharma; BMS; Celgene;

Pharmacyclics; TG Therapeutics

Research funding: Acerta Pharma; Celgene; Pharmacyclics; TG

Therapeutics

J. M. Melear

Other remuneration: Speaker's Bureau: AstraZeneca, Janssen

A. Yacoub

Other remuneration: Speaker's Bureau: Incyte

S. R. Fanning

Stock ownership: BMS, Abbvie, TG Pharma

Honoraria: BMS, Takeda, Abbvie, TG Pharma

Other remuneration: SPEAKER's BUREAU: BMS, Takeda, Sanoﬁ

D. J. Andorsky

Consultant or advisory role: Abbvie, BMS

Research funding: Celgene, Astra‐Zeneca, Epizyme

G. S. Nowakowski

Consultant or advisory role: Selvita, Debiopharm Group, Kite/Gilead,

Celgene, MorphoSys, Genentech

Research funding: Celgene, NanoString Technologies, MorphoSys

F. Lansigan

Consultant or advisory role: Celgene/BMS

Honoraria: Celgene/BMS

Research funding: Acrotech Pharmaceuticals

J. Li

Employment or leadership position: BMS

Stock ownership: BMS

Research funding: BMS

Educational grants: BMS

J. R. Ahn

Stock ownership: BMS

M. Gharibo

Stock ownership: BMS

M. Coleman

Stock ownership: immunomedics

Research funding: Abbvie, Bristol Myers, Celgene, Genentech, Gilead,

BeiGene, Innocare, Merck, Pfzier, Roche

TABLE 1Efﬁcacy for induction R

in patients with R/R MCL in MAGNIFY

SUPPLEMENT ABSTRACTS

109

SESSION 10: LYMPHOMA BIOLOGY 2

064 |THE TOPOLOGY OF MYC REARRANGEMENTS IN

DOUBLE‐HIT LYMPHOMA IS CONSTRAINED BY THE

PRECEDING IGH‐BCL2 REARRANGEMENT – AN LLMPP

PROJECT

L. K. Hilton

, B. Collinge

, S. Ben‐Neriah

, B. M. Grande

, G. W.

Slack

, P. Farinha

, T. Miyata‐Takata

, J. R. Cook

, G. Ott

A. Rosenwald

, E. Campo

, C. Amador

, T. C. Greiner

, P. W.

Raess

, J. Y. Song

, G. Inghirami

, E. S. Jaffe

, D. D. Weisen-

burger

, W. C. Chan

, H. Holte

, K. Beiske

, K. Fu

, J. Dela-

bie

, S. Pittaluga

, A. L. Feldman

, L. H. Sehn

, K. J. Savage

A. J. Mungall

, L. M. Staudt

, C. Steidl

, L. M. Rimsza

, R. D.

Morin

, D. W. Scott

BC Cancer, Centre for Lymphoid Cancer, Vancouver, Canada,

Sage

Bionetworks, Seattle, Washington, USA,

Niigata University Graduate

School of Medical and Dental Sciences, Division of Molecular and

Cellular Pathology, Niigata, Japan,

Cleveland Clinic, Department of

Molecular Pathology and Laboratory Medicine, Cleveland, Ohio, USA,

Robert‐Bosch‐Krankenhaus and Dr. Margarete Fischer‐Bosch Institute

of Clinical Pharmacology, Department of Clinical Pathology, Stuttgart,

Germany,

University of Wuerzburg, Institute of Pathology, Wuerzburg,

Germany,

Hospital Clinic, Department of Pathology, Barcelona, Spain,

University of Nebraska Medical Center, Department of Pathology and

Microbiology, Omaha, Nebraska, USA,

Oregon Health & Science Uni-

versity, Department of Pathology, Portland, Oregon, USA,

City of

Hope National Medical Center, Department of Pathology, Duarte, Cal-

ifornia, USA,

Weill Cornell Medicine, Pathology and Laboratory

Medicine, New York, New York, USA,

National Cancer Institute,

Laboratory of Pathology, Bethesda, Maryland, USA,

Oslo University

Hospital, Department of Oncology, Oslo, Norway,

Oslo University

Hospital, Department of Pathology, Oslo, Norway,

Roswell Park

Cancer Institute, Department of Pathology & Laboratory Medicine,

Buffalo, New York, USA,

University Health Network and University of

Toronto, Department of Laboratory Medicine and Pathobiology, Tor-

onto, Canada,

Mayo Clinic College of Medicine, Laboratory Medicine

and Pathology, Rochester, Minnesota, USA,

Canada's Michael Smith

Genome Sciences Centre, BC Cancer Research Institute, Vancouver,

Canada,

National Cancer Institute, Center for Cancer Research,

Bethesda, Maryland, USA,

Mayo Clinic Arizona, Department of Lab-

oratory Medicine and Pathology, Scottsdale, Arizona, USA,

Simon

Fraser University, Molecular Biology and Biochemistry, Burnaby,

Canada

Introduction: High‐grade B‐cell lymphoma with MYC and BCL2 and/

or BCL6 rearrangements (HGBL‐DH/TH) are aggressive tumors with

poor prognosis. In virtually all HGBL‐DH/TH‐BCL2 tumors, BCL2 is

rearranged to the variable region of the IGH locus, which is thought

to occur early in B‐cell differentiation during RAG‐mediated VDJ

recombination, leading to constitutive overexpression of BCL2 driven

by the potent IGH Eµenhancer. We explored the topology of MYC

rearrangements in double‐hit lymphomas compared with Burkitt

lymphoma (BL) and MYC single‐hit diffuse large B‐cell lymphoma

(DLBCL), to reveal patterns imposed by the preceding IGH‐BCL2

rearrangement.

Methods: We identiﬁed 112 HGBL‐DH/TH‐BCL2 and 55 de novo

DLBCL MYC single‐hit by break‐apart ﬂuorescence in situ hybrid-

ization, and included 96 MYC‐rearranged BL tumors as a com-

parison group. A combination of whole genome and capture

sequencing was used to identify MYC, BCL2 and BCL6 breakpoint

sequences. Sequencing data were aligned to hg38 with bwa‐mem,

and structural variants were called using Manta, GRIDSS, and

Delly. RNAseq data were quantiﬁed with Salmon and normalized

with variance stabilizing transformation to interrogate MYC

expression levels.

Results: The MYC breakpoint sequence was recovered in 77% of

tumors. Among BL and single‐hit DLBCL tumors, over 80% of MYC

rearrangements have an IGH partner, and less than 10% are part-

nered with IGL, IGK, or non‐IG loci (Figure 1). In contrast, only 35% of

MYC rearrangements in HGBL‐DH/TH‐BCL2 have an IGH partner,

while 21% have IGL and 40% have non‐IG partners (Figure 1). We

show that MYC expression is comparable among all IG and most

recurrent non‐IG partners. Strikingly, in HGBL‐DH/TH‐BCL2 with

IGH‐MYC, the rearrangement involved the previously rearranged

IGH‐BCL2 allele, and the breakpoints exclusively localized to the

recipient switch regions. This rearrangement leaves an intact Eµ

enhancer in proximity to BCL2 on a doubly rearranged IGH allele

while leaving the second IGH allele intact. In contrast, in BL and

single‐hit DLBCL the IGH‐MYC breaks were equally distributed to Sµ

(the donor IGHM switch region) and the recipient switch regions.

MYC expression was equivalent in tumors with Sµand recipient

switch region breakpoints.

Conclusions: This study demonstrates that the pattern of MYC

rearrangements in HGBL‐DH/TH‐BCL2 is constrained by the pres-

ence of IGH‐BCL2.MYC is infrequently rearranged to the IG variable

regions, supporting that MYC translocation is a class switch‐related

event that occurs later in lymphomagenesis. The observed MYC

rearrangements preserve both an intact IGH allele and the rela-

tionship between BCL2 and the IGH Eµenhancer. This leads to the

hypothesis that, at the time of acquiring the MYC rearrangement,

tumor survival is contingent on both intact B‐cell receptor expression

and the anti‐apoptotic activity of BCL2.

Keywords: Genomics, Epigenomics, and Other ‐Omics, Aggressive B‐

cell non‐Hodgkin lymphoma, Pathology and Classiﬁcation of

Lymphomas

No conﬂicts of interests pertinent to the abstract.

110

SUPPLEMENT ABSTRACTS

065 |THE MUTATIONAL LANDSCAPE OF DOUBLE/TRIPLE‐HIT

HIGH‐GRADE B‐CELL LYMPHOMA WITH BCL2

REARRANGEMENT (DH/TH‐BCL2) – AN LLMPP PROJECT

B. J. Collinge

, L. K. Hilton

, J. Wong

, S. Ben‐Neriah

, W. Alduaij

C. K. Rushton

, G. W. Slack

, P. Farinha

, T. Miyata‐Takata

, J. R.

Cook

, G. Ott

, A. Rosenwald

, E. Campo

, C. Amador

, T. C. Greiner

P. W. Raess

, J. Y. Song

, G. Inghirami

, E. S. Jaffe

, D. D. Wei-

senburger

, W. C. Chan

, H. Holte

, K. Beiske

, K. Fu

, J. Dela-

bie

, S. Pittaluga

, A. L. Feldman

, L. H. Sehn

, K. J. Savage

A. J. Mungall

, L. M. Staudt

, C. Steidl

, L. M. Rimsza

, R. D. Morin

D. W. Scott

BC Cancer, Centre for Lymphoid Cancer, Vancouver, Canada,

Simon

Fraser University, Molecular Biology and Biochemistry, Burnaby,

Canada,

Niigata University Graduate School of Medical and Dental

Sciences, Division of Molecular and Cellular Pathology, Niigata, Japan,

Cleveland Clinic, Department of Molecular Pathology and Laboratory

Medicine, Cleveland, Ohio, USA,

Robert‐Bosch‐Krankenhaus and Dr.

Margarete Fischer‐Bosch Institute of Clinical Pharmacology, Depart-

ment of Clinical Pathology, Stuttgart, Germany,

University of

Wuerzburg, Institute of Pathology, Wuerzburg, Germany,

Hospital

Clinic of the University of Barcelona, Department of Pathology, Bar-

celona, Spain,

University of Nebraska Medical Center, Department of

Pathology and Microbiology, Omaha, Nebraska, USA,

Oregon

Health & Science University, Department of Pathology, Portland,

Oregon, USA,

City of Hope National Medical Center, Department of

Pathology, Duarte, California, USA,

Weill Cornell Medicine, Pathology

and Laboratory Medicine, New York, New York, USA,

National

Cancer Institute, Laboratory of Pathology, Bethesda, Maryland, USA,

Oslo University Hospital, Department of Oncology, Oslo, Norway,

Oslo University Hospital, Department of Pathology, Oslo, Norway,

Roswell Park Cancer Institute, Department of Pathology & Labora-

tory Medicine, Buffalo, New York, USA,

University Health Network

and University of Toronto, Department of Laboratory Medicine and

Pathobiology, Toronto, Canada,

Mayo Clinic College of Medicine,

Laboratory Medicine and Pathology, Rochester, Minnesota, USA,

Cancer, Canada's Michael Smith Genome Sciences Centre, Vancouver,

Canada,

National Cancer Institute, Center for Cancer Research,

Bethesda, Maryland, USA,

Mayo Clinic, Department of Laboratory

Medicine and Pathology, Scottsdale, Arizona, USA

Introduction: The poor outcome of high‐grade B‐cell lymphoma with

MYC and BCL2 and/or BCL6 rearrangement (DH/TH) highlights the

need for identifying speciﬁc targetable biology. Although a gene

expression signature (DHITsig) shared by DH/TH‐BCL2 tumours has

conﬁrmed a uniﬁed biology, the genetic features of these tumours

beyond MYC/BCL2 rearrangement are not well established. Here, we

explore the mutational landscape of DH/TH‐BCL2 to identify key

molecular features that may inform on targetable tumour cell

vulnerabilities.

Methods: Diagnostic biopsies of 102 DH/TH‐BCL2 tumours

(morphology: 60 diffuse large B‐cell lymphoma (DLBCL); 42 high‐

grade – intermediate or blastoid) were identiﬁed with break‐

apart ﬂuorescent in situ hybridization (FISH). Tumours with

SUPPLEMENT ABSTRACTS

111

DLBCL morphology had no history of indolent lymphoma and were

sourced from BC Cancer where unbiased FISH testing was applied.

Among tumours of high‐grade morphology, 29% had a history of

indolent lymphoma. High conﬁdence somatic mutations (SNVs/

Indels) were identiﬁed on whole genome or exome sequencing

using an ensemble of variant callers (Strelka2, LoFreq, Mutect2,

SAGE). Mutation frequencies among recurrently mutated genes

were compared to Burkitt lymphoma (BL; Grande et al. Blood

2019) and GCB DHITsig‐neg DLBCL (Schmitz et al. NEJM 2018) to

identify genes with signiﬁcant differences in the recurrence of non‐

silent mutations (FDR <0.05). Genetic subtypes were assigned

using the LymphGen data portal.

Results: The most frequently mutated genes in DH/TH‐BCL2 were

in chromatin modiﬁers KMT2D,CREBBP, and EZH2, along with

BCL2 and TNFRSF14 – genes commonly mutated in follicular

lymphoma (FL) and EZB DLBCL. Consistently, 92% of tumours

were classiﬁed as EZB by LymphGen. Comparisons of DH/TH‐

BCL2 to GCB DHITsig‐neg DLBCL revealed less frequent alter-

ations of genes involved in NF‐κB signaling and immune surveil-

lance. Mutations in germinal centre dark zone (DZ) regulatory

genes FOXO1 and CCND3 were more frequent in DH/TH‐BCL2 –

genes that are also recurrently mutated in BL. While mutations in

NF‐κB signaling pathways and immune surveillance were also

uncommon in BL, these tumours were readily distinguishable from

DH/TH‐BCL2 by the absence of “FL‐like” mutations and more

frequent alterations to ID3,DDX3X,FBXO11,ARID1A, and

SMARCA4.

Conclusion: The similarity to FL is suggestive of an evolutionary

trajectory through an FL/FL‐like common progenitor, where DH/TH‐

BCL2 diverges from this trajectory by adopting a DZ‐like identity.

This is supported by near universal DHITsig positivity of both DH/

TH‐BCL2 and BL, suggesting this signature more accurately identiﬁes

a DZ biology that may be at least partly promoted by MYC rear-

rangement and mutations in FOXO1 and CCND3. Infrequent muta-

tions promoting immune escape in DH/TH‐BCL2 and BL is consistent

with a decreased selective pressure due to the “immune cold” nature

of the DZ.

Keywords: Genomics, Epigenomics, and Other ‐Omics, Aggressive B‐

cell non‐Hodgkin lymphoma, Pathology and Classiﬁcation of

Lymphomas

No conﬂicts of interests pertinent to the abstract.

066 |DO CELL‐OF‐ORIGIN, DOUBLE EXPRESSER, AND

DOUBLE HIT STATUS AFFECT OUTCOMES IN RELAPSED/

REFRACTORY DIFFUSE LARGE B CELL LYMPHOMA

(R/R DLBCL)? A PROSPECTIVE OBSERVATIONAL STUDY

S. H. Desai

, R. Mwangi

, M. Maurer

, R. King

, J. Cerhan

A. Feldman

, T. Habermann

, U. Farooq

, C. Thompson

, Y. Wang

S. M. Ansell

, T. E. Witzig

, G. N. Nowakowski

Mayo Clinic, Division of Hematology, Department of Medicine, Rochester,

Minnesota, USA,

Mayo Clinic, Department of Quantitative Health

Sciences, Rochester, Minnesota, USA,

Mayo Clinic, Department of

Quantitative Health Sciences, Rochester, Minnesota, USA,

Mayo Clinic,

Department of Laboratory Medicine and Pathology, Rochester, Minnesota,

USA,

Mayo Clinic, Division of Hematology, Department of Medicine,

Rochester, Minnesota, USA,

University of Iowa Hospitals and Clinics,

Department of Hematology, Oncology and Bone Marrow Transplant, Iowa

City, Iowa, USA

Introduction: Gene expression proﬁling classiﬁes DLBCL by cell of

origin (COO) into germinal center B cell (GCB) and activated B cell

(ABC) but a proportion of cases remain unclassiﬁed. Treatment‐naïve

GCB‐DLBCL have better outcomes. Double hit lymphoma (DHL)

deﬁned as high grade B cell lymphoma with rearrangements of MYC

and BCL2 or BCL6, and double expressor lymphoma (DEL) deﬁned as

DLBCL with co‐expression of BCL2 and MYC proteins, have poor

outcomes with frontline treatment. Impact of COO, DHL and DEL

status in R/R DLBCL is also not well‐characterized. We evaluated the

impact of these markers on outcomes of R/R DLBCL in a prospective

observational study.

Methods: Study cohort is derived from consecutive adult DLBCL

patients (pts) enrolled within 9 months of initial diagnosis into the

Molecular Epidemiology Resource (MER) cohort of the University of

Iowa/Mayo Clinic Lymphoma Specialized Program of Research

Excellence. Pts who relapsed after ﬁrst‐line therapy were included.

COO was available from immunohistochemistry (IHC) using Hans

algorithm and gene expression proﬁling (GEP) (Nanostring) on the

diagnostic FFPE biopsy. BCL2, MYC and BCL6 rearrangement were

done by FISH and protein expression was done by IHC. Pts were

followed for outcomes every 6 months from the date of diagnosis for

ﬁrst 3 years and then annually thereafter. Study objective was overall

survival (OS) from ﬁrst relapse.

Results: Of 373 pts with R/R DLBCL, 227 (61%) were male and

333 (93%) were white. At diagnosis, 278 (75%) had advanced

stage, 84 (23%) >1 extranodal sites, and 178 (48%) had interna-

tional prognostic index (IPI) ≥3. 278 pts had COO by IHC: 169

(60%) were GCB and 109 (40%) were non‐GCB. 140 had COO by

Nanostring: 44 (31%) were ABC, 72 (52%) were GCB, 13 (9%)

were unclassiﬁed and 11(8%) failed assay. 19 (5%) were DHL and

354 (95%) were non‐DHL. 34 (9%) had DEL, 115 (31%) were non‐

DEL and 224 did not have DEL status available. COO, either by

IHC [5 yr OS 31% (CI

: 24‐39) in GCB and 33% (CI

:25‐44) in

non‐GCB] or Nanostring [5 yr OS 31% (CI

: 22‐44) in GCB, 25%

(CI

: 14‐43) in ABC, 39% (CI

: 19‐77) in unclassiﬁed], was not

associated with difference in OS (Fig 1A‐B). DHL [2 yr OS 16

(CI

:6‐45) vs 43% (CI

: 39‐49), p <0.01] and DEL [5 yr OS 17%

(CI

: 8‐39) vs 33% (CI

: 25‐43), p =0.01] had lower OS than

non‐DHL and non‐DEL (1C&D).

Conclusions: COO at diagnosis by IHC or GEP does not impact

outcome of R/R DLBCL while DHL and DEL status were associated

with worse outcomes in R/R setting. Hence, evolving molecular

112

SUPPLEMENT ABSTRACTS

signatures of DLBCL beyond COO and interaction with tumor

microenvironment may be more important drivers of pathophysi-

ology of R/R DLBCL. While pattern of relapse, resistance to

chemotherapy and efﬁcacy of transplant need to be explored to

better characterize poor outcomes of R/R DHL and DEL, results of

this study will be helpful in design and interpretation of clinical

trials evaluating novel therapeutics in R/R DLBCL.

Keywords: Diagnostic and Prognostic Biomarkers, Aggressive B‐cell

non‐Hodgkin lymphoma

No conﬂicts of interests pertinent to the abstract.

067 |COPY NUMBER VARIATION ANALYSIS IDENTIFIES

DISTINCT GENOMIC FEATURES IN ADULT BURKITT LYMPHOMA

K. Dreval

, N. Thomas

, D. S. Gerhard

, L. K. Hilton

, J. Wong

J. S. Abramson

, N. L. Bartlett

, J. Bethony

, J. Bowen

, A. C. Bryan

C. Casper

, M. Dyer

, J. M. Gastier‐Foster

, B. M. Grande

T. Greiner

, N. B. Griner

, T. G. Gross

, N. L. Harris

, J. D. Irvin

E. Jaffe

, F. Leal

, J. P. Martin

, M.‐R. Martin

, S. M. Mbulaiteye

C. G. Mullighan

, A. J. Mungall

, K. Mungall

, C. Namirembe

A. Noy

, M. D. Ogwang

, J. Orem

, H. Petrello

, S. J. Reynolds

S. H. Swerdlow

, A. Traverse‐Glehen

, W. H. Wilson

M. A. Marra

, L. M. Staudt

, D. W. Scott

, R. D. Morin

Simon Fraser University, Department of Molecular Biology and

Biochemistry, Burnaby, Canada,

National Cancer Institute, National

Institutes of Health, Ofﬁce of Cancer Genomics, Bethesda, Maryland,

USA,

BC Cancer, Centre for Lymphoid Cancer, Vancouver, Canada,

Massachusetts General Hospital, Harvard Medical School, Center for

Lymphoma, Boston, Massachusetts, USA,

Washington University,

School of Medicine, St. Louis, Missouri, USA,

George Washington

University, Department of Microbiology, Immunology, and Tropical

Medicine, Washington, District of Columbia, USA,

Nationwide

Children's Hospital, The Abigail Wexner Research Institute, Columbus,

Ohio, USA,

Nationwide Children's Hospital, Biopathology Center,

Columbus, Ohio, USA,

Infectious Disease Research Institute, Seattle,

Washington, USA,

Frederick National Laboratory for Cancer Research

sponsored by the National Cancer Institute, Clinical Research

Directorate, Frederick, Maryland, USA,

Sage Bionetworks, Seattle,

Washington, USA,

University of Nebraska Medical Center,

Department of Pathology and Microbiology, Omaha, Nebraska, USA,

National Cancer Institute, National Institutes of Health, Center for

Global Health, Rockville, Maryland, USA,

Massachusetts General

Hospital, Harvard Medical School, Department of Pathology, Boston,

Massachusetts, USA,

Foundation for Burkitt Lymphoma Research,

Geneva, Switzerland,

National Cancer Institute, National Institutes of

Health, Laboratory of Pathology, Clinical Center, Bethesda, Maryland,

USA,

Instituto Nacional de Cancer Jose de Alencar, Programa de

Oncovirologia, Rio de Janeiro, Brazil,

National Cancer Institute,

Figure 1A: Overall survival‐COO by Hans method Figure 1B: Overall survival‐COO by Nanostring Figure 1C: Overall survival‐

DHL and non‐DHL Figure 1D: Overall survival‐DEL and non‐DEL

SUPPLEMENT ABSTRACTS

113

National Institutes of Health, Division of Cancer Epidemiology and

Genetics, Rockville, Maryland, USA,

St. Jude Children's Research

Hospital, Department of Pathology, Memphis, Tennessee, USA,

Canada's Michael Smith Genome Sciences Centre at BC Cancer,

Vancouver, Canada,

Uganda Cancer Institute, Kampala, Uganda,

Memorial Sloan Kettering Cancer Center and Weill Cornell Medical

College, New York, New York, USA,

St. Mary's Hospital Lacor,

EMBLEM Study, Gulu, Uganda,

National Institute of Allergy and

Infectious Diseases, National Institutes of Health, Division of Intramural

Research, Bethesda, Maryland, USA,

University of Pittsburgh School

of Medicine Presbyterian, Division of Hematopathology, Pittsburgh,

Pennsylvania, USA,

Hôpital Lyon Sud, Hospices Civils de Lyon,

Université Lyon 1, Service d'Anatomie Pathologique, Lyon, France,

Center for Cancer Research, National Cancer Institute, Lymphoid

Malignancies Branch, Bethesda, Maryland, USA

Introduction: Burkitt lymphoma (BL) is an aggressive B‐cell non‐

Hodgkin lymphoma that disproportionately affects populations in

malaria‐endemic regions. Although BL is curable, age is associated

with inferior clinical outcomes in most series, but the genetic basis of

response is unknown. Recent large efforts in the characterization of

pediatric BL (pBL) showed key genomic aberrations underlying dis-

ease progression. However, these studies have not focused on

structural abnormalities of a large number of adult BL (aBL). In this

study, we aimed to identify age‐speciﬁc genomic landscapes of copy

number variations (CNV) in BL.

Methods: Two cohorts comprising 124 pBL and 89 aBL patients,

representing both EBV‐positive and EBV‐negative cases within BL

Genomic Sequencing Project, were used in the study. Age cut‐off

between pBL and aBL was 20 years. In addition, genomes from 186

patients with diffuse large B‐cell lymphomas (DLBCL) were included

in our analysis for comparison. Somatic CNV were detected using

Battenberg and ControlFREEC algorithms.

Results: In BL, the proportion of genome altered by CNV was

signiﬁcantly lower when compared with DLBCL. This difference can

be attributed to the higher average length of CNV (P<0.0001) and

frequency of whole‐genome duplication (P<0.0001) in DLBCL. In

aBL speciﬁcally, ampliﬁcations within long arms of chromosomes 7,

10, 11, 15, 16, 19, and 20, or deletions affecting the short arm of

chromosome 9 were found at a higher frequency compared to pBL.

The ampliﬁed regions uniquely altered among aBL included genes

involved in the regulation of MYC function, such as KAT5, COPS6,

TRRAP, and PRMT1, suggesting they contribute to the MYC tran-

scriptional program. Importantly, aberrations within aBL‐speciﬁc re-

gions showed no difference when stratiﬁed on EBV status or patient

sex. In contrast, when patients are stratiﬁed based on EBV status,

EBV‐negative BL samples are uniquely associated with recurrent

ampliﬁcations within long arms on chromosomes 1 and 13, as well as

deletions at 6q15 and 11q25. The recurrent CNVs speciﬁc to EBV‐

negative BL are resulting in deletion of PRDM1 (identiﬁed in 6.9%

EBV‐negative aBL and not detected in EBV‐positive aBL) and

ampliﬁcation of the locus containing FCGR2B (found in 24.1% EBV‐

negative aBL and not identiﬁed in EBV‐positive aBL), a known

contributor to rituximab resistance in DLBCL and chronic lympho-

cytic leukemia.

Conclusions: We show that aBL has a distinct CNV proﬁle

compared to pBL, suggesting either distinct mutational processes or

selective pressures in this malignancy. These differences are not

explained when samples are stratiﬁed on EBV status or sex. aBL‐

speciﬁc CNVs affect genes that regulate or cooperate with MYC‐

mediated transactivation. In addition, we show that chromosomal

abnormalities affecting 1q, 6q, and 13q predominantly occur in

EBV‐negative BL.

Keywords: Genomics, Epigenomics, and Other ‐Omics, Tumor Biology

and Heterogeneity, Aggressive B‐cell non‐Hodgkin lymphoma

No conﬂicts of interests pertinent to the abstract.

068 |KEY GENETIC AND MOLECULAR ABERRATIONS

IDENTIFIED IN BOTH ADULT AND EBV‐POSITIVE BURKITT

LYMPHOMA PATIENTS

J. Orem

, M.‐R. Martin

, S. M. Mbulaiteye

, C. G. Mullighan

A. J. Mungall

, K. Mungall

, C. Namirembe

, A. Noy

, H. Petrello

M. D. Ogwang

, J.‐P. Martin

, S. J. Reynolds

, S. H. Swerdlow

A. Traverse‐Glehen

, W. H. Wilson

, M. A. Marra

, L. M. Staudt

D. W. Scott

, R. D. Morin

, G. Timothy

, M. Dryer

, K. Dreval

D. S. Gerhard

, L. K. Hilton

, J. S. Abramson

, N. L. Bartlett

J. Bethony

, J. Bowen

, A. Bryan

, C. Casper

, N. Thomas

J. M. Gastier‐Foster

, B. M Grande

, N. B. Griner

, T. G. Gross

N. L. Harris

, J. D. Irvin

, E. Jaffe

, F. Leal

Uganda Cancer Institute, Kampala, Uganda,

Foundation for Burkitt

Lymphoma Research, Geneva, Switzerland,

National Cancer Institute,

National Institutes of Health, Division of Cancer Epidemiology and

Genetics, Rockville, USA,

St. Jude Children's Research Hospital,

Department of Pathology, Memphis, USA,

BC Cancer, Canada's

Michael Smith Genome Sciences Centre, Vancouver, Canada,

Memorial

Sloan Kettering Cancer Center and Weill Cornell Medical College, New

York, USA,

Nationwide Children's Hospital, Pathology, Columbus, USA,

St. Mary's Hospital Lacor, EMBLEM Study, Gulu, Uganda,

National

Institute of Allergy and Infectious Diseases, National Institutes of

Health, Division of Intramural Research, Bethesda, USA,

University of

Pittsburgh School of Medicine Presbyterian, Division of

Hematopathology, Pittsburgh, USA,

Hôpital Lyon Sud, Hospices Civils

de Lyon, Université Lyon 1, Service d'Anatomie Pathologique, Lyon,

France,

Center for Cancer Research, National Cancer Institute,

Lymphoid Malignancies Branch, Bethesda, USA,

Center for Cancer

Research, National Cancer Institute, Lymphoid Malignancies Branch,

Bethesda, USA,

BC Cancer, Centre for Lymphoid Cancer, Vancouver,

Canada,

SFU, Molecular Biology and Biochemistry, Burnaby, Canada,

University of Nebraska Medical Center, Department of Pathology and

Microbiology, Omaha, USA,

Frederick National Laboratory for Cancer

Research sponsored by the National Cancer Institute, Clinical Research

Directorate, Frederick, USA,

National Cancer Institute, National

Institutes of Health, Ofﬁce of Cancer Genomics, Bethesda, USA,

114

SUPPLEMENT ABSTRACTS

Harvard Medical School, Center for Lymphoma, Massachusetts

General Hospital, Boston, USA,

Washington University, School of

Medicine, St. Louis, USA,

George Washington University, Department

of Microbiology, Immunology, and Tropical Medicine, Washington, USA,

Infectious Disease Research Institute, Infectious Disease Research

Institute, Seattle, USA,

The Ohio State University, Departments of

Pathology and Pediatrics, Columbus, USA,

Sage Bionetworks, Seattle,

USA,

National Cancer Institute, National Institutes of Health, Center

for Global Health, Rockville, USA,

Massachusetts General Hospital,

Harvard Medical School, Department of Pathology, Boston, USA,

SUPPLEMENT ABSTRACTS

115

Clinical Center, National Cancer Institute, National Institutes of

Health, Laboratory of Pathology, Bethesda, USA,

Instituto Nacional

de Cancer Jose de Alencar, Programa de Oncovirologia, Rio de Janeiro,

Brazil

Introduction: Burkitt lymphoma (BL) is the most common B‐cell

non‐Hodgkin lymphoma (NHL) in children accounting for ∼50%

of pediatric NHLs, while accounting for only 1‐2% of adult NHLs.

The genetic hallmark of BL is a translocation that places MYC

under the regulation of an immunoglobulin (IG) heavy or light

chain enhancer. Recently, we described molecular differences be-

tween EBV‐positive (EBV+) and EBV‐negative (EBV−) pediatric

BLs. Speciﬁcally, EBV +BLs are characterized by elevated

expression of activation‐induced cytidine deaminase, higher

genome‐wide mutation burden due to aberrant somatic hyper-

mutation, and fewer driver mutations per tumor. The limited

available studies comparing pediatric BL (pBL) to adult BL (aBL)

have revealed the latter more frequently harbor MYC‐IG light

chain rearrangements and possibly display some distinct driver

mutation proﬁles. The inferior survival rates of aBL patients ne-

cessitates the need for a better understanding of the full suite of

genetic and molecular features of aBL to enable more effective

treatments and prognostication within this population. Further,

important differences that distinguish EBV +BL tumors from

EBV−tumors have only recently been elucidated and the multi‐

faceted role EBV plays in BL pathogenesis remains incompletely

understood.

Methods: We performed whole genome sequencing and RNA‐seq on

205 BL tumors: 124(91 EBV+) pBL and 81(26 EBV+) aBL cases. We

analyzed mutation patterns to identify signiﬁcantly mutated genes

(SMGs) and compared their frequencies between EBV+/−BL and

aBL/pBL.

Results: We identiﬁed 4 SMGs not previously associated with BL:

TET2, HNRNPU, BRAF, and EZH2. Three of these are commonly

mutated in other cancers and at variable rates in diffuse large B‐

cell lymphoma. We speciﬁcally associate TET2 mutations with aBL

versus pBL (11% vs 1.6%, Q =0. 0.09)(Fig. 1A). TP53 mutations

were associated with signiﬁcantly inferior progression free survival

(PFS) in aBL at 2yr follow up (Fig. 1B). HNRNPU mutations have

not previously been linked to any cancer. These were mostly

truncating variants that track with EBV‐positivity (Fig. 1A), with

mutant cases having signiﬁcantly reduced expression of HNRNPU

mRNA.

Conclusion: This work highlights key mechanisms underlying BL

pathogenesis and key genetic differences based on age and EBV

status. We show the ﬁrst evidence of mutations in TET2, HNRNPU,

BRAF, and EZH2 being associated with BL, with TET2 mutations

speciﬁcally associated with aBL. Among the SMGs, TP53 mutations

were associated with inferior PFS in aBL, presenting a subset of

patients to be considered for novel treatment approaches. These

ﬁndings further elucidate differences between adult and pediatric

BL and highlight model systems for the further development of

novel therapeutics exploiting these differences.

The research was funded by: Burkitt Lymphoma Research, National

Cancer Institute and Canadian Institutes of Health Research

Keywords: Non‐Hodgkin (Pediatric, Adolescent, and Young

Adult)

No conﬂicts of interests pertinent to the abstract.

069 |TRIPLE POSITIVE (CD10 +BCL6 +MUM1+) DIFFUSE

LARGE B‐CELL LYMPHOMAS IN ADULTS ARE A

HETEROGENEOUS GROUP ENRICHED IN LARGE B‐CELL

LYMPHOMAS WITH IRF4 REARRANGEMENT

L. Frauenfeld

, N. Castrejon‐de‐Anta

, J. E. Ramis‐Zaldivar

, F. Otto

S. Streich

, J. Salmerón‐Villalobos

, A. Mayer

, J. Steinhilber

M. Pinyol

, B. Mankel

, I. Bonzheim

, F. Fend

, L. Rimza

I. Salaverria

, E. Campo

, O. Balagué

, L. Quintanilla‐Martinez

University of Tübingen, Institute for Pathology, Tübingen, Germany,

Hospital Clínic de Barcelona, Hematopathology Unit, Barcelona, Spain,

Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS),

Centro de Investigación Biomédica en Red de Cáncer (CIBERONC),

Barcelona, Spain,

Mayo Clinic, Division of Hematopathology, Phoenix,

AZ, USA

Introduction: Gene expression proﬁling (GEP) divides DLBCL ac-

cording to the cell of origin (COO) into GCB, ABC and unclassiﬁable

(UNC), exhibiting different mutational proﬁles. The Hans algorithm

(HA), a surrogate of GEP, classiﬁes cases expressing CD10, BCL6 and

MUM1 as GCB but it is not clear whether all these cases correspond

to GCB‐type. Accordingly, LBCL with IRF4 rearrangement (LBCL‐

IRF4) usually expresses a GCB phenotype (CD10+, BCL6+) together

with strong MUM1/IRF4. The aim of this study was to characterize

the molecular heterogeneity of DLBCL triple positive (CD10 +BCL6

+MUM1+) in adults.

Methods: Fifty‐ﬁve triple positive DLBCL were investigated with

FISH (BCL2, BCL6, MYC, IRF4, IGH, IGL), NGS targeted sequencing

(SureSelectXT, 66 genes), COO using Nanostring and/or HTG mo-

lecular, and copy number (CN) analysis using Oncoscan platform. The

mutational subtype was deﬁned using the algorithm by Wright et al

(Cancer Cell 2020).

Results: According to GEP, 32/54 (59%) cases were classiﬁed as

GCB, 17/54 cases (32%) as ABC, and 5/54 (9%) UNC. Based on

FISH analyses 3 groups were recognized. Group 1 included 15/55

cases (27%) without translocations. Eight cases (54%) were GCB‐,

whereas 7 cases ABC‐type (46%). The MCD mutational proﬁle

predominated in this group (6/12; 50%). Group 2 included 11/55

cases (20%) with isolated IRF4 alterations; 5 cases each were sub‐

classiﬁed either as GCB or ABC. This group was characterized by

one or multiple IRF4 mutations (82%) and frequent MYD88,

116

SUPPLEMENT ABSTRACTS

CARD11 and CD79B mutations. In two cases no IRF4 break was

identiﬁed; however, these two cases had a light chain IG break and

multiple IRF4 mutations. Group 3 included 29/55 cases (53%) with

one or several translocations in BCL2/BCL6/MYC/IGH. Two of these

cases had a complex FISH constellation with BCL2 and/or BCL6

together with IRF4 translocation. In this group predominated the

GCB‐type (19/29; 66%) and the EZB (8/25; 32%) mutational pro-

ﬁle. Oncoscan was performed in 7 cases of LBCL‐IRF4. A total of

118 genetic alterations were identiﬁed (mean: 17 CNA/case). The

comparison between LBCL‐IRF4 in adults and previously published

data in pediatric population (ﬁgure) showed no difference in terms

of recurrent CN regions; however, adult cases showed higher ge-

netic complexity (17 vs 6.25 alt/case; P =0.33) and more often

ABC COO (P =0.05). Mutational comparison showed higher

mutational load in adult cases (10.6 vs 4.7 mutation/case; P =

0.004) and higher frequency of KMT2D, MYD88 and BTG2 muta-

tions (P <0.05).

Conclusion: 1) Triple positive DLBCL is a heterogeneous group that

should not be classiﬁed with the HA. 2) Triple positive DLBCL in

adults are enriched in LBCL‐IRF4 (20%) and show frequent IRF4

mutations, which are absent in other groups. 3) LBCL‐IRF4 in adults is

more often ABC‐type and shows higher genetic complexity when

compared with the pediatric counterpart.

Keywords: Pathology and Classiﬁcation of Lymphomas

No conﬂicts of interests pertinent to the abstract.

SESSION 11: HODGKIN LYMPHOMA

070 |CIRCULATING TUMOR DNA IS A PROGNOSTIC

BIOMARKER IN CLASSIC HODGKIN LYMPHOMA

V. Spina

, M. C. Pirosa

, A. Bruscaggin

, A. Condoluci

, K. Pini

G. Forestieri

, I. Zangrilli

, M. di Trani

, M. Kurlapski

, A. Moccia

R. Moia

, P. Bulian

, S. Annunziata

, E. Borsatti

, M. Rodari

G. Romanowicz

, G. M. Sacchetti

, M. Faderl

, R. Koch

D. Piffaretti

, L. Terzi di Bergamo

, A. Stasia

, M. Cittone

SUPPLEMENT ABSTRACTS

117

S. Chauvie

, G. Stüssi

, B. Gerber

, A. Stathis

, S. Gillessen

Sommer

, F. Cavalli

, E. Zucca

, V. Gattei

, J. M. Zaucha

A. Pinto

, G. Gaidano

, C. Carlo‐Stella

, S. Hohaus

, L. Ceriani

D. Rossi

Institute of Oncology Research, Division of Experimental Hematology,

Bellinzona, Switzerland,

Oncology Institute of Southern Switzerland,

Division of Hematology, Bellinzona, Switzerland,

Fondazione Policlinico

Universitario Agostino Gemelli IRCCS, Department of diagnostic imaging,

oncological radiotherapy and hematology, Rome, Italy,

Humanitas

Clinical and Research Center, Humanitas Cancer Center, Milan, Italy,

Medical University of Gdańsk, Department of Hematology and

Transplantology, Gdańsk, Poland,

Oncology Institute of Southern

Switzerland, Clinic of Medical Oncology, Bellinzona, Switzerland,

University of Eastern Piedmont, Division of hematology, Novara, Italy,

Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Clinical and

Experimental Onco‐Hematology Unit, Aviano, Italy,

Università Cattolica

del Sacro Cuore, Institute of Nuclear Medicine, Rome, Italy,

IRCCS CRO,

Nuclear Medicine, Aviano, Italy,

Humanitas Clinical and Research

Center, IRCCS, Unit of Nuclear Medicine, Milan, Italy,

Medical Univer-

sity of Gdansk, Department of Nuclear Medicine, Gdansk, Poland,

“Maggiore della Carità” Hospital, Nuclear Medicine, Novara, Italy,

Santa Croce e Carle Hospital, Department of Medical Physics, Cuneo,

Italy,

National Cancer Institute, Fondazione “G. Pascale” IRCCS,

Hematology‐Oncology and Stem Cell transplantation Unit, Naples, Italy,

Imaging Institute of Southern Switzerland, Clinic of Nuclear Medicine

and Molecular Imaging, Bellinzona, Switzerland

Introduction: Current prognostic models of classic Hodgkin lym-

phoma (cHL) incorporate pre‐treatment clinical and laboratory

parameters, but have low discrimination capacity and limited clinical

utility. Circulating tumor DNA (ctDNA) is a sensitive cancer

biomarker, but its clinical validity in cHL is unknown. Here we tested

whether pre‐treatment ctDNA qualiﬁcation and quantiﬁcation is

prognostic in cHL.

Methods: The IOSI‐EMA‐003 (NCT03280394) is a prospective,

observational, multicentric, international, non‐interventional trial in

which liquid biopsy samples were collected from newly diagnosed

cHL patients at the following time points: baseline, interim and end of

treatment PET/CT assessments. The LyV4.0 ctDNA CAPP‐seq assay

(sensitivity: 0.1%) was used to qualify and quantify ctDNA. Clinical

data quality was assured through remote medical monitoring. Base-

line, interim and end of treatment PET/CT are undergoing central

review.

Results: A total of 135 patients were recruited. Baseline charac-

teristics were those expected in unelected, previously untreated

cHL. After a median follow‐up of 33 months, 25 patients had

progression events, accounting for 3‐year progression free survival

(PFS) of 80.0%. At baseline, ctDNA was detected in 90% of pa-

tients, with an average of 27 somatic mutation reporters per case.

A summary of genes affected by nonsynonymous, synonymous, and

noncoding somatic mutations is shown in Figure A. Median ctDNA

load was 358.5 hGE/mL of plasma (range 0‐16572.4), and corre-

lated (p =0.004) with clinical proxies of the tumor volume (Figure

B). None of the genes mutated in ≥5% of patients, including TP53,

stratiﬁed PFS (Figure C). By recursive partitioning, ctDNA load in

baseline samples stratiﬁed PFS with an optimized threshold of

1500 hGE/mL of plasma (Figure D). Patients with high pre‐

treatment levels of ctDNA had signiﬁcantly inferior rates of 3‐

118

SUPPLEMENT ABSTRACTS

year PFS (44.4% vs 86.9% p =0.000006) than those with low

levels (Figure E). High pre‐treatment levels of ctDNA occurred: i)

in 0% of early, 12.2% of intermediate and 15.9% of advanced cHL;

and ii) in 6.0% of 0‐2 international prognostic score (IPS) and

27.3% of >3 IPS cHL. Levels of pre‐treatment ctDNA marked

patients’ outcome, irrespective of whether they presented in in-

termediate or advanced stage. The combination of high pre‐

treatment ctDNA and poor IPS risk >3 allowed to sort out

upfront poor risk cHL showing a 3‐year PFS of only 33.3% (Figure

F). In multivariable analysis, the interaction between pre‐treatment

ctDNA and IPS remained prognostic for PFS (HR 7.3, 95% CI 3.0‐

17.5, p =0.00009) when controlling for GHSG risk. PFS prediction

metrics (c‐index) were 64.9% for ctDNA, 66.2% for IPS and 69.8%

for IPS combined to ctDNA.

Conclusions: ctDNA load is a strong, independent prognostic factor

in cHL. Next studies should aim at the external validation of this

biomarker and to its integration with radiomics.

The research was funded by: ‐Fond’Action, Lausanne, Switzerland;

‐Translational Research Program, No. 6594‐20, The Leukemia &

Lymphoma Society, New York

Keywords: Diagnostic and Prognostic Biomarkers, Hodgkin

lymphoma

Conﬂicts of interests pertinent to the abstract

A. Moccia

Consultant or advisory role: Roche, Janssen and Takeda

D. Rossi

Honoraria: AbbVie, AstraZeneca, Janssen

Research funding: AbbVie, AstraZeneca, Janssen.

071 |RELAPSES IN INTERIM PET NEGATIVE LIMITED STAGE

HODGKIN LYMPHOMA PATIENTS RECEIVING ABVD WITH OR

WITHOUT RADIOTHERAPY–ANALYSIS OF EORTC/FIL/LYSA H10

AND UK NCRI RAPID TRIALS

I. Aurer

, A. Neven

, V. Fiaccadori

, N. Counsell

, E. Phillips

L. Clifton‐Hadley

, C. Fortpied

, M. Andre

, M. Federico

S. Barrington

, T. Illidge

, J. Radford

, J. Raemaekers

University Hospital Centre Zagreb, Division of Hematology, Department

of Internal Medicine, Zagreb, Croatia,

European Organisation for

Research and Treatment of Cancer, Lymphoma Group, Brussels, Belgium,

University College London, Cancer Institute, London, UK,

University

College London, Cancer Research UK and University College London

Cancer Trials Centre, London, UK,

University of Manchester, The Christie

NHS Foundation Trust and NIHR Manchester Biomedical Research

Centre, Manchester, UK,

Université Catholique de Louvain, Department

of Hematology, Yvoir, Belgium,

University of Modena and Reggio Emilia,

CHIMOMO Department, Modena, Italy,

King's College London, King's

College London and Guy's and St Thomas' PET Centre, London, UK,

Radboud University Medical Centre, Department of Hematology,

Nijmegen, Netherlands

Introduction: Randomized trials H10 and RAPID were designed to

assess whether radiotherapy (RT) can be safely omitted in newly

diagnosed limited‐stage Hodgkin lymphoma (HL) patients who are

interim PET‐negative (iPETneg) after 2 (H10) or 3 (RAPID) cycles of

ABVD. Despite differences in inclusion criteria and treatment, in both

studies relapses were more frequent after chemotherapy only (C)

than after combined modality treatment (C+RT), even in iPETneg

patients. A recent exploratory analysis of the H10 study showed that

most relapses after C occurred in the ﬁrst 2 years after treatment

(early relapses) and were observed in initially involved areas. Male

sex and stage II were negative prognostic factors in H10. We sought

to conﬁrm these ﬁndings in the independent data set of the RAPID

trial.

Patients and Methods: Patients enrolled in the RAPID trial were

assigned retrospectively to a favorable (F) or unfavorable (U) prog-

nostic group according to the EORTC/GELA criteria. First, the timing

and site of relapses were analyzed descriptively in the F group. The

low number of relapses in the U group prevented a reliable com-

parison with the H10 counterpart. Next, RAPID (F+U groups) was

analyzed with a Cox model adjusted for age, sex and stage to esti-

mate the treatment hazard ratio (HR) and its 95% conﬁdence interval

(CI). Finally, H10 and RAPID (F+U groups) were combined in a Cox

model stratiﬁed by study, with a different HR before and after 2

years.

Results: Patient numbers, group allocation and outcomes are pre-

sented in table 1. In the RAPID F group, relapses after C occurred

within 2 years in 11 patients and after that in 2; and after C+RT in 2

and 4 patients, respectively. Relapses after C occurred only in initially

involved areas in 6 patients, only in uninvolved areas in 2 and in both

in 5; and after C+RT, in 1, 2 and 3 patients, respectively. In RAPID (F

+U groups), the effect of gender and stage went in the same direction

as in H10 but was non‐signiﬁcant. In the combined analysis, the

hazard of relapses was signiﬁcantly lower after C+RT than after C

during the ﬁrst 2 years (HR =0.20, 95% CI =(0.11, 0.37)) but similar

from 2 years onwards (HR =0.84, 95%CI =(0.41, 1.69)). The ﬁtted

model showed a signiﬁcant prognostic effect of gender (worse

prognosis for males) and stage (worse prognosis for stage II), mainly

driven by H10.

Conclusions: The independent validation with RAPID and the com-

bined analysis conﬁrm the H10 ﬁnding that omitting RT in iPET neg.

patients treated with C results in an increase in early relapses.

Moreover, in both studies, relapses after C were more frequently

conﬁned to initially involved areas alone.

Keywords: Hodgkin lymphoma, Radiation Therapy

No conﬂicts of interests pertinent to the abstract.

SUPPLEMENT ABSTRACTS

119

072 |CALGB 50801 (ALLIANCE): PET ADAPTED

THERAPY IN BULKY STAGE I/II CLASSIC HODGKIN

LYMPHOMA (CHL)

A. S. LaCasce

, T. Dockter

, A. Ruppert

, L. Kostakoglu

, H. Schöder

E. D. Hsi

, J. A. Bogart

, B. D. Cheson

, N. D. Wagner‐Johnston

J. S. Abramson

, K. J. Maddocks

, J. P. Leonard

, N. L. Bartlett

Dana Farber Cancer Institute, Medical Oncology, Boston, USA,

Alliance Statistics and Data Center, Mayo Clinic, Rochester, USA,

Alliance Statistics and Data Center, The Ohio State University,

Columbus, USA,

University of Virginia, Radiology and Medical Imaging,

Charlottesville, USA,

Memorial Sloan Kettering Cancer Institute,

Molecular Imaging and Therapy Service, New York, USA,

Wake Forest

University Health Science, Pathology, Winston‐Salem, USA,

SUNY

Upstate Medical University, Radiation Oncology, Syracuse, USA,

Lym-

phoma Research Foundation, Scientiﬁc Advisory Board Member, New

York, USA,

The Sidney Kimmel Comprehensive Cancer Center at Johns

Hopkins, Oncology, Baltimore, USA,

Massachusetts General Hospital

Cancer Center, Hematology/Oncology, Boston, USA,

Ohio State Uni-

versity Wexner Medical Center, Columbus, OH, Hematology, Columbus,

USA,

Meyer Cancer Center, Weill Cornell Medical College, Hematol-

ogy and Medical Oncology, New York, USA,

Washington University

School of Medicine in St. Louis and Siteman Cancer Center, Medical

Oncology, St. Louis, USA

Background: Bulky disease is associated with inferior outcomes in

patients with early stage cHL. Historically, most patients (pts)

receive chemotherapy followed by radiotherapy (RT), which is

associated with long‐term toxicity. We tested a PET‐adapted

approach to reduce the need for RT in pts with early PET‐

negative (PET‐) disease and escalate therapy in pts with PET‐

positive (PET+) disease.

Methods: Eligible pts aged 18‐60 years (yrs) had stage IA‐IIB cHL

with disease bulk >10 cm or >.33 max intrathoracic diameter on

chest x‐ray. Pts received 2 cycles of doxorubicin‐bleomycin‐

vinblastine‐dacarbazine (ABVD) followed by centrally reviewed

PET. PET‐was deﬁned as Deauville of 1‐3. Pts who achieved a

negative PET scan (PET2‐) received 4 additional cycles of ABVD.

PET2+pts received 4 cycles of escBEACOPP plus 30 Gy involved‐

site radiation therapy. The primary endpoint was progression‐free

survival (PFS) estimated from PET2. With 93 pts and assuming

30% PET2+, there was 80% power to rule out that PFS of PET2+

pts was substantially inferior to PFS of PET2‐pts (HR 4.1, 3‐yr

PFS 40% vs 80%) if the true PFS of PET2+pts was closer to

that of PET2‐pts (HR 2.29, 3‐yr PFS 60% vs 80%) with one‐sided

alpha =0.15. With few events and mature follow‐up, we report

results 3 yrs after the last pt was enrolled.

Results: Between May 2010 and October 2017, 101 pts enrolled.

Excluding 6 ineligible pts (3 without baseline DLCO, 2 did not

meet deﬁnition of bulk, 1 stage IIIB) and 1 pt without PET2, 94

were evaluable. 78% of pts were PET2‐(73 PET2‐, 21 PET2+).

Median age was 30 yrs (range: 18 to 58) and 53.2% were female.

Distribution of stage was: 1A ‐7.4%, IB ‐2.1%, IIA – 39.4%, IIB ‐

51.1%; 61.9% PET2+pts had stage IIB disease. Therapy was

generally well tolerated. Grade >3 neutropenia occurred in 86%

of pts with 8% of PET2‐and 10% of PET2+with grade >3 febrile

neutropenia. 3‐yr PFS estimates were 93.1% (95% CI: 87.4‐99.1%)

in PET2‐pts, 89.7% (95% CI: 77.2‐100.0%) in PET2+pts (HR =

1.01, 85% upper bound 2.32), and 92.3% (95% CI: 87.0‐98.0%) for

all pts. The protocol‐deﬁned primary endpoint was met as the PFS

hazard ratio for PET2+vs PET2‐was less than 4.1 (one sided p =

0.04). With a median follow‐up of 5.5 yrs, 3 PET2‐pts died (HL,

anaplastic astrocytoma and COPD) and 1 PET2+died of pro-

gressive disease. 3‐yr overall survival (not a primary or secondary

outcome of the study) estimates were 98.6% (95% CI: 95.9‐

100.0%) in PET2‐pts, 94.4% (95% CI: 85.4‐100.0%) in PET2+pts

(HR: 1.2, 95% CI: 0.12, 11.60), and 97.7% (95% CI: 94.7‐100.0%)

for all pts.

Conclusions: Excellent PFS outcomes were observed in all pts using a

PET‐adapted approach that allowed omission of RT in 78% of pts. In

addition, PET2+pts treated with escalation to BEACOPP and con-

solidative RT did not have inferior outcomes.

EA ‐previously submitted to ASCO 2021

The research was funded by: Support: U10CA180821,

U10CA180882; https://acknowledgments.alliancefound.org

Keywords: Hodgkin lymphoma

No conﬂicts of interests pertinent to the abstract.

TABLE 1Number, group allocation

and outcome of patients randomized in

the H10 and RAPID trials

F U Unclassiﬁed*

C+RT C C+RT C C+RT C

H10 randomized 227 238 292 302 0 0

relapsed 2 (1%) 30 (13%) 16 (5%) 30 (10%) 0 0

RAPID randomized 118 123 65 63 25 25

relapsed 6 (5%) 13 (11%) 3 (5%) 5 (8%) 0 3 (12%)

mainly due to missing ESR.

120

SUPPLEMENT ABSTRACTS

073 |NEW PROGNOSTIC SCORE INCORPORATING MTV

PREDICTS TREATMENT FAILURE IN ADVANCED HODGKIN

LYMPHOMA

S. F. Barrington

, A. A. Kirkwood

, L. C. Pike

, C. Guezennec

, H. Li

M. le Blanc

, D. Poon

, M. V. Knopp

, L. Clifton‐Hadley

, C. Lau-

bach

, H. Schöder

, J. W. Friedberg

, P. W. Johnson

Kings College London and Guy's and St Thomas' PET Centre, School of

Biomedical Engineering and Imaging Sciences, King's College London,

King's Health Partners, London, UK,

University College London, Cancer

Research UK and University College London Cancer Trials Centre,

London, UK,

Kings College London, Kings College London and Guy's

and St Thomas' PET Centre, London, UK,

Kings College London, Kings

College London and Guy's and St Thomas' PET Centre, London, UK,

Fred Hutchinson Cancer Research Center, SWOG Statistics and

Data Management Center, Seattle, USA,

Fred Hutchinson Cancer

Research Center, SWOG Statistics and Data Management Center,

Seattle, USA,

Ohio State University, IROC Ohio, Wright Center of

Innovation, Columbus, USA,

Ohio State University, IROC Ohio, Wright

Center of Innovation, Columbus, USA,

University College London,

Cancer Research UK and University College London Cancer Trials

Centre, London, UK,

SWOG Cancer Research Network, Operations

Ofﬁce, San Antonio, Texas, USA,

Memorial Sloan Kettering

Cancer Center, Department of Radiology, New York, USA,

University

of Rochester, JWF Wilmot Cancer Institute, Rochester, USA,

University of Southampton, Department of Medical Oncology,

Southampton, UK

Background: The risk of treatment failure in Hodgkin lymphoma (HL)

might be assessed more accurately by incorporating presentation

features such as disease severity using FDG‐PET characteristics to

guide the intensity of initial therapy.

Methods: Twenty‐four baseline clinical and PET factors were

evaluated in the UK RATHL

population including metabolic

tumour volume (MTV), tumor lesion glycolysis and SUV metrics.

The association of factors with the risk of a HL event, deﬁned as a

positive interim PET scan at cycle 2 of ABVD, or relapse after a

negative interim scan, was explored using bootstrapping with Cox

regression and receiver operating characteristic‐area under the

curve (ROC‐AUC) analysis (5‐year event) to derive a new prog-

nostic score. The score developed in a training set (n =521) was

tested in an internal validation set (n =261) and an independent

trial dataset of stage III‐IV HL pts (SWOG S0816

, n =333). MTV

using SUV≥4 was selected; Cox regression p ≤0.05 in 97.2% of

samples and highest ROC‐AUC in the majority of samples. Other

factors were included if they remained in a backwards selection

model in ≥50% of samples.

Results: The ﬁnal model included MTV, lymphocytes as percentage of

total white cells and stage IV disease. Hazard ratio (HR) for a HL

event was 2.72 per unit increase in prognostic score (p <0.001), ROC

AUC: 0.65. The high risk group was chosen to be the 30% of pts with

the highest scores, considering various cut points in the training set

for acceptable risks for escalation of initial therapy.

HL 5‐year event rates were 22.1% and 45.4% for standard and

high risk pts respectively HR:2.40, p <0.001,(sensitivity 48%,

speciﬁcity 76.3%). 5‐year PFS for standard risk pts was 85.1%.

The new score discriminated better than IPS 0‐2 vs 3+(sensi-

tivity 43.5%, speciﬁcity 68.1%), 22.6% pts would be incorrectly

deemed high risk using IPS compared to 17.5% with the new

score. For 1000 patients treated with ABVD by 5 years, 125/300

pts with a high risk score vs. 127/353 pts with IPS 3+would

have a HL event. Conversely 564/700 pts with a standard

risk score vs. 481/647 with IPS 0‐2 would not experience a HL

event.

Combining the score with IPS provided no additional information

(Figure). The score validated in the internal and independent datasets

with results for stage III and IV pts from S0816 and RATHL (training

set) of: ROC‐AUC 0.62 and 0.61, sensitivity 57.1% and 55.5%,

speciﬁcity 57.6% and 60.7%, HR 1.66 (p =0.005) and 1.90 (p =

0.001); median follow up was 7 and 5.5 years for S0816 and RATHL

respectively.

Conclusion: This new prognostic score can be used to identify pts in

whom a more intensive initial therapy than ABVD would be most

useful, whilst avoiding escalation for those with a high chance of cure

with ABVD alone. As the score is continuous, the cut point could be

changed depending on the proposed therapy and the risk/reward

balance for over/under treatment.

N Engl J Med 2016;374:2419‐29

Blood 2019;134:1238‐46

The research was funded by: National Institute for Health Research

and Social Care RP‐2‐16‐07‐001, Cancer Research UK (CRUK/07/

033)

Keywords: Diagnostic and Prognostic Biomarkers, PET‐CT, Hodgkin

lymphoma

Conﬂicts of interests pertinent to the abstract

A. A. Kirkwood

Research funding: Millennium pharmaceutics inc., Bristol‐Myers

Squibb Pharmaceuticals Ltd., Amgen GmBbH., Celgene Ltd., Merck

Sharp and Dohme Ltd., Janssen‐Cilag Ltd, Pﬁzer Ltd.

L. Clifton‐Hadley

Research funding: Millennium pharmaceutics inc., Bristol‐Myers

Squibb Pharmaceuticals Ltd., Amgen GmBbH., Celgene Ltd., Merck

Sharp and Dohme Ltd., Janssen‐Cilag Ltd, Pﬁzer Ltd.

SUPPLEMENT ABSTRACTS

121

074 |NIVOLUMAB FOR RELAPSED OR REFRACTORY (R/R)

CLASSICAL HODGKIN LYMPHOMA (CHL) AFTER AUTOLOGOUS

TRANSPLANTATION: 5‐YEAR OVERALL SURVIVAL FROM THE

PHASE 2 CHECKMATE 205 STUDY

S. M. Ansell

, P. J. Bröckelmann

, G. von Keudell

, H. J. Lee

A. Santoro

, P. L. Zinzani

, G. P. Collins

, J. B. Cohen

, J. P. De Boer

J. Kuruvilla

, K. J. Savage

, M. Trneny

, M. Provencio

U. Jaeger

, W. Willenbacher

, R. Swanink

, M. Sacchi

M. A. Shipp

, A. Engert

, P. Armand

Mayo Clinic, Division of Hematology, Rochester, Minnesota, USA,

University Hospital of Cologne, Department of Internal Medicine,

Cologne, Germany,

Memorial Sloan Kettering Cancer Center,

Department of Hematology, New York, New York, USA,

University of

Texas MD Anderson Cancer Center, Department of Lymphoma and

Myeloma, Houston, Texas, USA,

Humanitas University, Humanitas

Cancer Center, Rozzano–Milan, Italy,

University of Bologna, Institute

of Hematology L. e A. Seràgnoli, Bologna, Italy,

Churchill Hospital,

Oxford Cancer and Haematology Centre, Oxford, UK,

Emory Univer-

sity, Winship Cancer Institute, Atlanta, Georgia, USA,

Antoni van

Leeuwenhoek Hospital, Netherlands Cancer Institute, Amsterdam,

Netherlands,

University of Toronto and Princess Margaret Cancer

Centre, Division of Medical Oncology and Hematology, Toronto, Can-

ada,

BC Cancer, Department of Medical Oncology, Vancouver, Can-

ada,

Charles University in Prague and General University Hospital in

Prague, Department of Haematology, Prague, Czech Republic,

Hos-

pital Universitario Puerta de Hierro, Department of Medical Oncology,

Madrid, Spain,

Medical University of Vienna, Clinical Department for

Hematology and Hemostaseology, Vienna, Austria,

Innsbruck Medical

University, Department of Internal Medicine V, Innsbruck, Austria,

Bristol Myers Squibb, Global Biometrics and Data Sciences, Braine

l’Alleud, Belgium,

Bristol Myers Squibb, Global Drug Development,

Princeton, New Jersey, USA,

Dana‐Farber Cancer Institute, Depart-

ment of Medical Oncology, Boston, Massachusetts, USA,

University

Hospital of Cologne, Department of Internal Medicine, Cologne, Ger-

many,

Dana‐Farber Cancer Institute, Department of Medical

Oncology, Boston, Massachusetts, USA

Introduction: PD‐1 immune checkpoint inhibitors, including the

monoclonal antibody nivolumab (NIVO), have shown strong activity

122

SUPPLEMENT ABSTRACTS

in patients (pts) with R/R cHL. The pivotal phase 2 CheckMate 205

study (NCT02181738) demonstrated an objective response rate

(ORR) of 69%, a median duration of response (DOR) of 17 mo, and

median progression‐free survival (PFS) of 15 mo in pts with R/R cHL

treated with NIVO after autologous hematopoietic cell trans-

plantation (auto‐HCT), with a median follow‐up of 18 mo (Armand

et al. J Clin Oncol 2018). Recently, PD‐1 inhibitor monotherapy

showed signiﬁcantly improved PFS vs brentuximab vedotin (BV) in R/

R cHL (Kuruvilla et al. ASCO 2020). However, long‐term survival

beneﬁt of anti–PD‐1 therapy and optimal duration of treatment (tx)

are unknown. We present updated results of CheckMate 205 with a

median follow‐up of 58 mo.

SUPPLEMENT ABSTRACTS

123

Methods: CheckMate 205 enrolled pts with R/R cHL after auto‐HCT

failure into cohorts by tx history: BV‐naive (cohort A), BV after auto‐

HCT (cohort B), and BV before and/or after auto‐HCT (cohort C). Pts

received NIVO 3 mg/kg every 2 wk until disease progression or un-

acceptable toxicity. Pts in cohort C discontinued nivo after 1 y in

complete remission (CR) and could resume if they relapsed within 2 y.

The primary endpoint was ORR per independent radiologic review

committee (IRRC); other endpoints included CR, DOR, PFS, overall

survival (OS), and safety.

Results: Overall, 243 pts were treated (63, 80, and 100 in cohorts A,

B, and C, respectively). Baseline characteristics were previously

described. Median duration of tx was 14 mo. ORR was 71% (95% CI,

65–77) with a CR rate of 21%. Median PFS was 15 mo (95% CI, 11–

19) and median DOR was 18 mo (95% CI, 15–26). Pts with CR had

longer median PFS (37 mo) and DOR (30 mo) than pts with partial

remission (PR; 15 and 13 mo, respectively). The 2‐y and 5‐y OS rates

(95% CI) were 87% (82–91) and 71% (65–77), and PFS rates were

37% (30–44) and 18% (12–25), respectively. Pts with CR also had

improved OS; failure to achieve disease control was a poor prog-

nostic factor for OS (Figure). Per protocol, 12 pts in cohort C stopped

study tx after ≥1 y of CR. At time of analysis, after a median of 48

mo (range 36–55) from last tx, 6 pts were still in response; 3 were re‐

treated with NIVO after disease progression (2 re‐achieved CR and 1

PR). No new toxicities were observed, and the most common tx‐

related adverse events (TRAEs) of any grade were fatigue (25%),

diarrhea (17%), and rash (12%), almost all grade 1–2. Grade 3–4

TRAEs occurred in 68 pts (28%). TRAEs led to discontinuation in

26 pts (11%). There were no tx‐related deaths.

Conclusions: This 5‐y analysis of CheckMate 205 cohorts ABC

demonstrated a favorable OS and conﬁrms the efﬁcacy and safety of

NIVO for pts with cHL who progressed or relapsed after auto‐HCT.

The safety proﬁle is similar to previous reports. It appears feasible to

stop NIVO after 1 y of CR and re‐initiate tx upon disease progression.

The research was funded by: Bristol Myers Squibb

Keywords: Hodgkin lymphoma, Immunotherapy

Conﬂicts of interests pertinent to the abstract

S. M. Ansell

Research funding: Bristol Myers Squibb, Takeda, Seagen, AI Thera-

peutics, Regeneron, Trillium, Afﬁmed, ADC Therapeutics

P. J. Bröckelmann

Consultant or advisory role Takeda

Honoraria: Bristol Myers Squibb, Takeda

Research funding: BeiGene, Bristol Myers Squibb, Merck Sharp &

Dohme, Takeda

Educational grants: Celgene

H. J. Lee

Consultant or advisory role Bristol Myers Squibb, Kite Pharma

Honoraria: Aptitude Health, Pharmacyclics, Cancer Experts, Guide-

point Global

Research funding: Bristol Myers Squibb/Celgene, Takeda, Seattle

Genetics, Janssen, Merck, Oncternal, Onyx

A. Santoro

Consultant or advisory role Bristol Myers Squibb, Servier, Gilead,

Pﬁzer, Eisai, Bayer, Merck Sharp & Dohme, Arqule, Sanoﬁ

Other remuneration: Speaker's bureau: Takeda, Bristol Myers

Squibb, Roche, AbbVie, Amgen, Celgene, Servier, Gilead, AstraZe-

neca, Pﬁzer, Arqule, Lilly, Sandoz, Eisai, Novartis, Bayer, Merck

Sharp & Dohme

P. L. Zinzani

Consultant or advisory role Servier, Merck, Janssen, Eusapharma,

Takeda, Incyte, Gilead, Novartis

Honoraria: Servier, Merck, Janssen, Eusapharma, Takeda, Incyte,

Gilead, Novartis

G. P. Collins

Consultant or advisory role Bristol Myers Squibb, Merck Sharp &

Dohme, Gilead, Roche, Takeda, Incyte, Daiichi Sankyo, BeiGene,

Novartis, ADC Therapeutics

Honoraria: Bristol Myers Squibb, Merck Sharp & Dohme, Gilead,

Roche, Takeda, Incyte, Daiichi Sankyo, BeiGene, Novartis, ADC

Therapeutics

Research funding: Bristol Myers Squibb, Merck Sharp & Dohme,

Celleron, BeiGene, Amgen, Pﬁzer

J. B. Cohen

Consultant or advisory role BeiGene, Pharmacyclics, Adaptive, Apti-

tude Health, Gilead/Kite, Adicet, AstraZeneca

Research funding: Bristol Myers Squibb/Celgene, Novartis, Gen-

entech, Takeda, LAM, Loxo/Lilly, AstraZeneca, BeiGene

J. Kuruvilla

Consultant or advisory role Abbvie, Bristol Myers Squibb, Gilead,

Karyopharm, Merck, Roche, Seattle Genetics

Honoraria: Amgen, Antengene, AstraZeneca, Bristol Myers Squibb,

Gilead, Incyte, Janssen, Karyopharm, Merck, Novartis, Pﬁzer, Roche,

Seattle Genetics, TG Therapeutics

Research funding: Canadian Cancer Society, Leukemia and Lym-

phoma Society Canada, Princess Margaret Cancer Foundation,

Janssen, Roche, AstraZeneca

Other remuneration: Karyopharm (DSMB)

K. J. Savage

Consultant or advisory role Bristol Myers Squibb, Merck, Seattle

Genetics, Gilead, AstraZeneca, Novartis, Janssen, Kyowa, Servier

Other remuneration: Steering committee: BeiGene

M. Trneny

Consultant or advisory role Roche, Takeda, Bristol Myers Squibb,

Incyte, Abbvie, Amgen, Gilead Sciences, Janssen, MorphoSys, Novartis

Honoraria: Roche, Janssen, Gilead Sciences, Takeda, Bristol Myers

Squibb, Amgen, Abbvie, MorphoSys, Novartis

Educational grants: Gilead Sciences, Bristol Myers Squibb, Roche,

Janssen, Abbvie, Takeda

M. Provencio

Consultant or advisory role Bristol Myers Squibb, Merck Sharp &

Dohme, AstraZeneca, Takeda, Roche, Lilly

124

SUPPLEMENT ABSTRACTS

Research funding: Bristol Myers Squibb, Roche

U. Jaeger

Consultant or advisory role Bristol Myers Squibb, Celgene

Honoraria: Bristol Myers Squibb, Celgene

R. Swanink

Employment or leadership position: Bristol Myers Squibb

M. Sacchi

Employment or leadership position: Bristol Myers Squibb

M. A. Shipp

Consultant or advisory role Immunitas Therapeutics, AstraZeneca

Research funding: Bristol Myers Squibb, Merck, Bayer, AbbVie

A. Engert

Consultant or advisory role Takeda, ADC Therapeutics, Tessa

Pharmaceuticals

Honoraria: Bristol Myers Squibb, Takeda, Novartis, Merck Sharp &

Dohme, ONO Pharma, Hexal, AstraZeneca

Research funding: Bristol Myers Squibb, Takeda, Afﬁmed

P. Armand

Consultant or advisory role Merck, Bristol Myers Squibb, Pﬁzer,

Afﬁmed, Adaptive, ADC Therapeutics, Celgene, Morphosys, Daiichi

Sankyo, Miltenyi, Tessa, GenMab, C4, Enterome, Regeneron, Epi-

zyme, AstraZeneca, Genentech

Honoraria: Merck, Bristol Myers Squibb

Research funding: Merck, Bristol Myers Squibb, Afﬁmed, Adaptive,

Genentech, IGM, Kite

075 |CAMIDANLUMAB TESIRINE EFFICACY AND SAFETY IN

AN OPEN‐LABEL, MULTICENTER, PHASE 2 STUDY OF PATIENTS

(PTS) WITH RELAPSED OR REFRACTORY CLASSICAL HODGKIN

LYMPHOMA (R/R CHL)

P. L. Zinzani

, C. Carlo‐Stella

, M. Hamadani

, A. F. Herrera

S. M. Ansell

, J. Radford

, K. Maddocks

, J. Kline

, K. J. Savage

N. L. Bartlett

, P. F. Caimi

, Y. Negievich

, H. G. Cruz

, L. Wang

J. Wuerthner

, G. P. Collins

IRCCS Azienda Ospedaliero‐Universitaria di Bologna Istituto di Ema-

tologia “Seràgnoli”, and Dipartimento di Medicina Specialistica, Diag-

nostica e Sperimentale, Università di Bologna, Bologna, Italy,

Humanitas Clinical and Research Center – IRCCS, and Humanitas

University, Department of Oncology and Hematology, Rozzano, Milan,

Italy,

Medical College of Wisconsin, BMT & Cellular Therapy Program,

Department of Medicine, Milwaukee, Wisconsin, USA,

City of Hope

Comprehensive Cancer Center, Department of Hematology & Hemato-

poietic Cell Transplantation, Duarte, California, USA,

Mayo Clinic,

Division of Hematology, Rochester, Minnesota, USA,

NIHR Manchester

Clinical Research Facility, The Christie NHS Foundation Trust and

University of Manchester, Manchester Academic Health Science Centre,

Manchester, UK,

Ohio State University Medical Center, Division of

Hematology, Columbus, Ohio, USA,

The University of Chicago,

Department of Medicine, Chicago, Illinois, USA,

BC Cancer and Uni-

versity of British Columbia, Department of Medical Oncology, Van-

couver, BC, Canada,

Washington University School of Medicine in St

Louis, Division of Oncology, St Louis, Montana, USA,

University

Hospitals Cleveland Medical Center/Case Western Reserve University,

Department of Medicine, Cleveland, Ohio, USA,

ADC Therapeutics SA,

Clinical Development, Epalinges, Switzerland,

ADC Therapeutics

America, Inc, Clinical Development, Murray Hill, New Jersey, USA,

Churchill Hospital, NIHR Oxford Biomedical Research Centre, Oxford

Cancer and Haematology Centre, Oxford, UK

Introduction: Camidanlumab tesirine (Cami) is an antibody‐drug

conjugate comprising a human IgG1 anti‐CD25 monoclonal anti-

body conjugated to a pyrrolobenzodiazepine (PBD) dimer warhead.

Cami has demonstrated encouraging antitumor activity and

manageable toxicity in a Ph 1 trial in lymphomas, particularly R/R

cHL. Here we present preliminary results of a Ph 2 study of Cami

monotherapy in pts with R/R cHL.

Methods: Pts with R/R cHL and ≥3 prior therapy lines, including

brentuximab vedotin (BV) and PD‐1 blockade (≥2 lines if ineligible

for hematopoietic cell transplantation; HCT) were enrolled

(NCT04052997). An interim analysis was conducted after meeting a

protocol‐speciﬁed criterion for pausing enrollment (Herrera et al.

Blood 2020;136:Suppl.1:21–3). After safety and efﬁcacy review, the

pause was lifted. The primary objective is evaluation of Cami efﬁcacy

by overall response rate (ORR; central review). Duration of response

(DOR) and progression‐free survival (PFS) are secondary efﬁcacy

endpoints. Efﬁcacy is reported for pts on study for ≥12 weeks since

ﬁrst dose. Safety endpoints include frequency and severity of TEAEs,

assessed in all treated pts. Pts received Cami 45 μg/kg IV on Day 1 of

each 3‐week cycle for 2 cycles, then 30 μg/kg for subsequent cycles.

Results: As of Dec 4, 2020, 82 pts with R/R cHL had enrolled. Pts had

received a median of 7 (range 3–19) prior lines of therapy. Pts

received a mean (SD) of 4 (3.0) Cami cycles. Five of 47 (10.6%) pts

who discontinued treatment underwent HCT following Cami

administration.

In the 52 pts evaluable for efﬁcacy, ORR was 82.7% (43/52 pts), with

38.5% (20/52) pts attaining complete response (Figure). Median DOR

was not reached at median (range) follow‐up of 9.2 (2.0–14.3

[censored]) months. Median (95% CI) PFS was 9.2 (5.0–not reached)

months.

All‐grade TEAEs in ≥25% of 82 pts in the safety analysis set were

fatigue (34, 41.5%), nausea and maculopapular rash (each 23,

28.0%) and pyrexia (21, 25.6%). Grade ≥3 TEAEs in ≥5% pts were

hypophosphatemia (7, 8.5%) and lymphopenia (5, 6.1%). TEAEs

leading to Cami dose delay/reduction or discontinuation occurred

in 8 (9.8%) and 10 (12.2%) pts, respectively. Categories of TEAEs

considered PBD‐associated included skin reactions/nail disorders

(48, 58.5%), liver function test abnormalities (23, 28.0%) and

SUPPLEMENT ABSTRACTS

125

edema/effusion (10, 12.2%). Guillain–Barré syndrome (GBS)/poly-

radiculopathy was reported in 4 (4.9%) pts: GBS in 2 pts (Grade 2,

resolved; Grade 4, improved); radiculopathy in 1 pt (Grade 2,

resolved); and encephalitis and polyneuropathy in 1 pt (Grade 3,

ongoing).

Conclusions: Cami demonstrated high ORR in heavily pretreated R/R

cHL after failure of BV and PD‐1 blockade, with encouraging DOR.

Data continue to mature. Safety remains consistent with prior ﬁnd-

ings. Pt enrollment completed on Jan 29, 2021 and updated results

for the total population (N =117) will be presented.

The research was funded by: ADC Therapeutics SA

Keywords: Hodgkin lymphoma, Chemotherapy, Immunotherapy

Conﬂicts of interests pertinent to the abstract

P. L. Zinzani

Consultant or advisory role: Verastem, MSD, Eusapharma, and

Sanoﬁ, ADC Therapeutics, Celltrion, Gilead, Janssen‐Cilag, Bristol‐

Myers Squibb, Servier, Sandoz, TG Therapeutics, Takdea, Roche,

Eusapharma, and Kyowa Kirin

C. Carlo‐Stella

Consultant or advisory role: ADC Therapeutics, Roche, Sanoﬁ, Kar-

yopharm Therapeutics, Celgene/Bristol‐Myers Squibb, Incyte

Honoraria: Bristol‐Myers Squibb, Merck Sharp & Dohme, Janssen

Oncology, AstraZeneca, Celgene, Takeda, Incyte, Gilead Sciences

Research funding: ADC Therapeutics

M. Hamadani

Consultant or advisory role: Consultancy services for Janssen

R&D, Incyte Corporation, ADC Therapeutics, Celgene Corporation,

Pharmacyclics, Omeros, AbGenomics, Verastem and TeneoBio;

speaker's bureau for Sanoﬁ Genzyme, BeiGene and AstraZeneca

Research funding: Takeda Pharmaceutical Company, Spectrum

Pharmaceuticals and Astellas Pharma

A. F. Herrera

Consultant or advisory role: Bristol‐Myers Squibb; Genentech/

Roche; Merck; Seattle Genetics; Karyopharm

Research funding: Bristol‐Myers Squibb (Inst.); Genentech/Roche

(Inst.); Immune Design (Inst.); Merck (Inst.); Pharmacyclics (Inst.);

Seattle Genetics (Inst.)

Other remuneration: Travel/accommodation/expenses: Bristol‐

Myers Squibb

S. M. Ansell

Research funding: ADC Therapeutics, Bristol Myers Squibb, Seattle

Genetics, Afﬁmed, Regeneron, Trillium, AI Therapeutics

J. Radford

Consultant or advisory role: Takeda, ADC Therapeutics, Bristol‐

Myers Squibb, Novartis and Kite Pharma; speaker for Takeda, ADC

Therapeutics and Seattle Genetics

Stock ownership: ADC Therapeutics and AstraZeneca (spouse)

Honoraria: Expert testimony for Takeda and ADC Therapeutics

Research funding: Takeda

K. Maddocks

Consultant or advisory role: ADC Therapeutics, AstraZeneca, BMS, Cel-

gene, Gilead, Karyopharm, Morphosys, Pharmacyclics, Seattle Genetics

Research funding: BMS

J. Kline

Consultant or advisory role: Merck, Kite/Gilead, Verastem, Mor-

phoSys, Karyopharm, Seagen

Research funding: Merck, Verastem, iTeos

K. J. Savage

Consultant or advisory role: Merck, BMS, Seattle Genetics, Gilead,

AstraZeneca, Novartis, Janssen, Kyowa, Servier

Honoraria: Merck, BMS, Seattle Genetics, Gilead, AstraZeneca,

Novartis, Janssen, Kyowa

FIGURE 1 Best overall responses in patients

with classical Hodgkin lymphoma (efﬁcacy

analysis set

)

126

SUPPLEMENT ABSTRACTS

Research funding: Roche (Institutional)

Other remuneration: Beigene (Steering Committee)

N. L. Bartlett

Consultant or advisory role: ADC Therapeutics, Autolus, Bristol‐Myers

Squibb, Celgene, Forty Seven, Immune Design, Janssen, Kite Pharma,

Merck, Millennium, Pﬁzer, Pharmacyclics, Roche/Genentech, Seattle

Genetics

Research funding: ADC Therapeutics

P. F. Caimi

Consultant or advisory role: Research support from ADC Therapeutics,

and Genentech; advisory boards for ADC Therapeutics, Genentech,

Kite Pharmaceuticals, Verastem, Seattle Genetics, and Amgen; con-

sultancy services for TG Therapeutics; speaker's bureau for Celgene

Y. Negievich

Employment or leadership position: ADC Therapeutics SA

Stock ownership: ADC Therapeutics SA

H. G. Cruz

Employment or leadership position: ADC Therapeutics SA

Stock ownership: ADC Therapeutics SA

L. Wang

Employment or leadership position: ADC Therapeutics America, Inc

Stock ownership: ADC Therapeutics America, Inc

J. Wuerthner

Employment or leadership position: ADC Therapeutics SA

Stock ownership: ADC Therapeutics SA

G. P. Collins

Consultant or advisory role: ADC Therapeutics, Roche, Takeda, BMS,

MSD, Celleron, Beigene, Gilead, Novartis, Daiichi Sankyo, Incyte and

Celgene

Research funding: Celgene, Amgen, MSD, BMS, and Celleron

SESSION 12: INDOLENT LYMPHOMAS

076 |INTRATUMORAL T‐CELLS HAVE A DIFFERENTIAL IMPACT

ON FDG‐PET PARAMETERS IN FOLLICULAR LYMPHOMA

K. Nath

, Soi‐C. Law

, D. Talaulikar

, M. B. Sabdia

, J. Gunawardana

L. M. de Long

, M. Shanavas

, H. Tsang

, J. W. Tobin

, S.‐J. Halliday

A. Hernandez

, D. Cross

, R. Bird

, S. Jain

, C. Keane

, J. Trotman

P. Law

, M. K. Gandhi

Mater Research Institute, University of Queensland, Brisbane, Australia,

Haematology Translational Research Unit, Canberra Hospital, Canberra,

Australia,

Princess Alexandra Hospital, Department of Haematology,

Brisbane, Australia,

Canberra Hospital, Department of Anatomical

Pathology, Canberra, Australia,

Concord Repatriation General Hospital,

Department of Haematology, Sydney, Australia,

Princess Alexandra

Hospital, Department of Medical Imaging, Brisbane, Australia

Introduction: Results of the prognostic impact of the pre‐therapy

FDG‐PET parameters TMTV (3D tumor burden of all involved sites)

and SUV

max

(highest FDG‐uptake within a single lesion) in follicular

lymphoma (FL) are conﬂicting and appear to vary between chemo-

immunotherapy regimens. Similarly, the predictive utility of pre‐

therapy T‐effector genes is reversed between patients treated with

‘CHOP/CVP’‐R/O and those treated with B‐R/O (Bolen, Blood, 2021).

Notably, B‐R (unlike R‐CHOP) causes profound/sustained T‐cell

depletion. The relationship between intratumoral T‐cells and PET pa-

rameters is unknown.

Methods: A comprehensive molecular and functional analysis was

undertaken in 83 patients with de‐novo Grade I‐IIIa FL.

Results: Low intratumoral T‐cell gene expression (by NanoString) was

associated with ∼6‐fold higher TMTV (41%SUV

max

and ﬁxed SUV>2.5

thresholds) and ∼7‐fold higher TLG (total lesional glycolysis) (Fig 1A‐

B). Consistent with this, FL nodes with increased malignant B‐cell

inﬁltration (by ﬂow cytometry) showed high TMTV (Fig 1C). Since T‐

cell clonal inﬁltration of the tumor microenvironment (TME) is prog-

nostic in FL (Tobin, JCO, 2019), we reasoned that clonal expansions

within intratumoral T‐cell compartments may reﬂect differential

TMTV. To test this, we FACS sorted T‐cells from de‐aggregated nodes

into CD8

(activated, exhausted, resting) and CD4

(T‐follicular helper

], T‐regulatory [T

REG

], non‐T

REG

CD4

cells) intratumoral T‐

cell subsets. High TMTV patients had fewer clonally expanded acti-

vated CD8

and CD4

cells (by TCR sequencing) than low TMTV

patients (Fig 1D‐E). Next, to directly compare glucose‐uptake between

B‐and T‐cells, a ﬂuorescently labelled glucose analogue (2‐NBDG) ﬂow

cytometry assay was performed. Glucose‐uptake was higher in CD4

and CD8

T‐cells than in intratumoral B‐cells (Fig 1F). However, as

CD19

B‐cells contributed ∼2/3

rds

of the total lymphocytes, they

contribute most to overall glucose‐uptake (Fig 1G), demonstrating that

TMTV reﬂects the burden of the malignant population. To test SUV

max

we interrogated a unique subset of 12 patients in whom pre‐biopsy PET

scans were available. This allowed comparison of the TME gene

expression proﬁle of the excised node with its corresponding pre‐biopsy

SUV

max:

(‘lesional SUV

max

’), thereby accounting for the impact of SUV

on tumor spatial heterogeneity. Lesional SUV

max

associated with CD4

and CD8A, but not CD19 (Fig 1H).

Conclusion: TMTV best reﬂects the malignant FL B‐cell burden,

whereas intratumoral T‐cells inﬂuence SUV

max

. This may contribute to

the contradictory results between the prognostic role of different PET

parameters, particularly between short and long‐term T‐cell depleting

chemoimmunotherapeutic regimens. The impact of glucose‐uptake in

intratumoral T‐cells should be considered when interpreting pre‐

therapy FDG‐PET in FL.

The research was funded by: This work was supported by a Hae-

matology Society of Australia and New Zealand and Leukaemia

Foundation PhD scholarship (KN); and the Leukaemia Foundation,

the Mater Foundation and the National Health and Medical Research

Council (MKG). The Translational Research Institute is supported by

the Australian Government.

Keywords: Metabolism, PET‐CT, Indolent non‐Hodgkin lymphoma

No conﬂicts of interests pertinent to the abstract.

SUPPLEMENT ABSTRACTS

127

FIGURE 1 (A): TMTV in patients with a T‐cell

and T‐cell

RICH

inﬂitrative state (T‐cell status was deﬁned by a standardized CD4 +CD8A

gene score). (B) TLG in patients with a T‐cell

and T‐

RICH

tumor inﬂitrate. (C) TMTV in patients with a low vs. high intratumoral FL B‐cell

inﬂitrateb (by ﬂow cytometry) (D) Intratumoral CD8

and CD8

cell subset speciﬁc TCR repertoire clonality according to TMTV status. CD8

cells were FACS sorted into activated (PD‐1

LAG3

-ve

), exhausted (PD‐1

LAG3

-ve

) and resting (PD‐

-ve

LAG3

-ve

subsets. (E) TCR repertoire

clonality in patients with a low vs. high TMTV within TILS sorted into CD4

subsets: CXCR5

ICOS

T‐foilicular helper (T

cells,

CD25

CD127

CXCR5

-ve

regulatory T‐cells (T

REG

) and CD4

non‐T

REG

subsets. (F) Cellular glucose uptake within intratumoral CD19

CD8

and CD4

cells. (G) Lymphocyte contribution to overall glucose‐uptake after normalizing for % live cells. Avg. cell inﬂitration : CD19

64% CD8

4% and CD4

18%. (H) Lymphocyte (CD19,CD8A,CD4) gene expression reported according to the pre‐biopsy ‘lesional

SUX

max

’state

128

SUPPLEMENT ABSTRACTS

077 |DIRECT‐ACTING ANTIVIRALS AS PRIMARY TREATMENT

FOR HCV‐ASSOCIATED INDOLENT NON‐HODGKIN

LYMPHOMAS: THE PROSPECTIVE BART STUDY OF THE

FONDAZIONE ITALIANA LINFOMI

M. Merli

, S. Rattotti

, M. Spina

, F. Re

, M. Motta

, F. Piazza

L. Orsucci

, Andrés J. M. Ferreri

, O. Perbellini

, A. Dodero

D. Vallisa

, A. Pulsoni

, A. Santoro

, V. Zuccaro

, E. Chimienti

F. Russo

, C. Visco

, A. L. Zignego

, L. Marcheselli

, S. Luminari

M. Paulli

, R. Bruno

, L. Arcaini

University Hospital “Ospedale di Circolo e Fondazione Macchi” ‐ASST

Sette Laghi, University of Insubria, Hematology, Varese, Italy,

Fondazione IRCCS Policlinico San Matteo, Hematology, Pavia, Italy,

Centro di Riferimento Oncologico, IRCCS, Medical Oncology and

Immune‐related Tumors, Aviano (PN), Italy,

Azienda Ospedaliera Uni-

versitaria, Hematology and BMT Center, Parma, Italy,

ASST Spedali

Civili Brescia, Hematology, Brescia, Italy,

Azienda Ospedaliera‐

Universitaria, University of Padova, Medicine, Hematology, Padova,

Italy,

Città della Salute e della Scienza di Torino, Hematology, Torino,

Italy,

IRCCS San Raffaele Scientiﬁc Institute, Lymphoma Unit, Milan,

Italy,

San Bortolo Hospital, Hematology Unit, Vicenza, Italy,

Fon-

dazione IRCCS Istituto Nazionale dei Tumori, Hematology, Milano, Italy,

Ospedale Guglielmo da Saliceto, Hematology, Piacenza, Italy,

Sapienza University of Rome, Translational and Precision Medicine,

Roma, Italy,

Humanitas Research Hospital, Medical Oncology and

Hematology Unit, Rozzano, Milan, Italy,

Fondazione IRCCS Policlinico

San Matteo, University of Pavia, Infectious and Tropical Diseases,

Pavia, Italy,

University of Verona, Medicine, Section of Hematology,

Verona, Italy,

University of Florence, Clinical and Experimental

Medicine, Interdepartmental Hepatology Center MASVE, Florence, Italy,

Fondazione Italiana Linfomi ONLUS, FIL, Modena, Italy,

AUSL ‐

IRCCS Reggio Emilia, University of Modena and Reggio Emilia, Hema-

tology, Reggo Emilia, Italy,

Fondazione IRCCS Policlinico San Matteo,

University of Pavia, Anatomic Pathology Unit, Pavia, Italy,

University

of Pavia, Molecular Medicine, Pavia, Italy

Introduction: The most convincing argument for the role of hepatitis

C virus (HCV) in the pathogenesis of some indolent non‐Hodgkin

lymphoma (iNHL) subtypes, especially marginal‐zone lymphomas

(MZL), is represented by retrospective observations of tumor

regression after viral eradication by interferon (IFN)‐free direct‐

acting antivirals (DAAs). However, no prospective studies in this

setting have been performed so far.

Methods: In 2016 the Fondazione Italiana Linfomi started the pro-

spective, multicenter, phase 2 BArT study (NCT02836925), evalu-

ating IFN‐free DAAs regimens in untreated, HCV‐RNA+, non‐

cirrhotic, iNHL patients (pts) without criteria for immediate con-

ventional treatment. Pts with genotypes (GT) 1 and 4 received

ledipasvir (LDV)/sofosbuvir (SOF) for 12 (naïve) or 24 weeks (IFN

experienced), GT 2 pts SOF +ribavirin (RBV) for 12 weeks and GT

3 pts LDV/SOF +RBV for 24 weeks. After amendment (Jul 2017),

GT 2 and 3 pts received the novel SOF/velpatasvir (VEL) regimen

for 12 weeks. The primary objective was sustained virological

response (SVR) while the main secondary objectives were overall

response rate (ORR) of lymphoma, progression‐free survival (PFS)

and toxicity.

Results: Forty pts (17 males, 23 females) were enrolled, including 27

MZL (14 MALT, 9 nodal and 4 splenic), 6 lymphoplasmacytic lym-

phoma (LPL), 4 CD5‐negative iNHL not otherwise speciﬁed (NOS), 2

small lymphocytic lymphoma (SLL) and 1 grade (g) 2 follicular lym-

phoma (FL). Median age was 68 years (yrs) (45‐83). Stage was III/IV

in 34 pts (85%). Extranodal sites were involved in 14 (40%) and bone

marrow in 23 pts (58%). GT was 1 in 17 (43%), 2 in 21 (52%), 3 in 2

pts (5%). Four pts (10%) previously failed an IFN‐based regimen. All

pts received GT‐appropriate DAAs: 17 LDV/SOF, 8 SOF +RBV, 15

SOF/VEL. The primary endpoint was met as all patients achieved

SVR (100%). DAAs were well tolerated, with 17 pts (43%) experi-

encing 30 g 1‐2 (including 2 RBV‐related g 1 anemia) and 2 g 3‐4

adverse events (g 4 lipase increase; g 3 breast cancer). ORR of

lymphoma was 45%, including 8 pts (20%) achieving complete

response (CR) and 10 (25%) partial response (PR), while 16 (40%)

exhibited stable disease (SD) and 6 (15%) progressed (Tab 1). No

signiﬁcant difference in ORR was recorded between MZL and non‐

MZL cases (48 vs 33%, p =0.74). Among MZL, the best ORR was

evidenced in MALT MZL (71%). At a median follow‐up of 33 months

(95% CI 21‐39) no pt died, 3 additional pts progressed, with a 3‐yr

PFS of 80% (95% CI 64‐89%, Fig 1) and 3‐yr duration of response

for CR/PR pts of 83%.

Conclusions: This is the ﬁrst prospective trial investigating the role of

DAAs in HCV+iNHL pts not requiring immediate conventional

TABLE 1

Response Histology Total (%)

CD5‐NOS SLL LPL FL MZL

CR 1 ‐ ‐ ‐ 7 8 (20)

PR 1 1 1 1 6 10 (25)

ORR 2 1 1 1 13 18 (45)

SD 1 ‐5‐10 16 (40)

PD 1 1 ‐ ‐ 4 6 (15)

Total 4 2 6 1 27 40

SUPPLEMENT ABSTRACTS

129

treatment. Our results suggest that HCV eradication with DAAs

should be considered as ﬁrst‐line therapy in this setting.

The research was funded by: Gilead Sciences, Inc

Keywords: Indolent non‐Hodgkin lymphoma, Therapeutics and Clin-

ical Trials in Lymphoma ‐Other

Conﬂicts of interests pertinent to the abstract

A. J. M. Ferreri

Consultant or advisory role: Gilead Sciences, Inc

Research funding: Gilead Sciences, Inc

A. Santoro

Consultant or advisory role: Gilead Sciences, Inc

Other remuneration: Gilead Sciences, Inc

R. Bruno

Consultant or advisory role: Gilead Sciences, Inc

L. Arcaini

Consultant or advisory role: Gilead Sciences, Inc

Research funding: Gilead Sciences, Inc

Other remuneration: Gilead Sciences, Inc

078 |PRIMARY EXTRANODAL FOLLICULAR LYMPHOMA IN A

LARGE RETROSPECTIVE SURVEY OF THE INTERNATIONAL

EXTRANODAL LYMPHOMA STUDY GROUP (IELSG31)

A. Conconi

, B. Vannata

, A. Janikova

, A. Ramirez

, C. Lobetti

Bodoni

, G. Nowakowski

, M. Mian

, Andrés J. M. Ferreri

, G. Ryan

G. A. Pangalis

, M. E. Cabrera

, S. Luminari

, S. Montoto

R. Tsang

, I. Aurer

, C. Visco

, L. Mazzucchelli

, M. Trneny

G. Gaidano

, M. Federico

, A. Lopez‐Guillermo

, B. Pro

E. Zucca

Azienda sanitaria locale Biella, Ospedale degli Infermi ‐Ematologia,

Biella, Italy,

Oncology Institute of Southern Switzerland, Medical

Oncology Clinic, Bellinzona, Switzerland,

University Hospital Brno,

Department of Hematology and Oncology, Brno, Czech Republic,

Instituto Nacional de Cancerologia, Hematology Department, Mexico

City, Mexico,

Mayo Clinic, Division of Hematology, Rochester, Minnesota,

USA,

Ospedale di Bolzano, Ematologia e Centro Trapianto Midollo Osseo,

Bolzano, Italy,

IRCCS San Raffaele Scientiﬁc Institute, Unità Operativa di

Oncologia Medica, Milano, Italy,

Peter MacCallum Cancer Institute,

Deptment of Radiation Oncology, Melbourne, Australia,

Athens Medical

Center‐Psychikon Branch, Hematology Department, Athens, Greece,

Hospital del Salvador, Facultad de Medicina, Santiago, Chile,

Arcis-

pedale Santa Maria Nuova, Servizio di Ematologia, Reggio Emilia, Italy,

St. Bartholomew's Hospital, Department of Medical Oncology, London,

UK,

University Health Network, Princess Margaret Hospital, Toronto,

Canada,

University Hospital Centre Zagreb, Division of Hematology,

Zagreb, Croatia,

University of Verona, Departmento of Medicine ‐

Section of Hematology, Verona, Italy,

Istituto Cantonale di Patologia,

EOC, Locarno, Switzerland,

Charles University General Hospital Prague,

First Faculty of Medicine, Prague, Czech Republic,

Azienda Ospedaliera

“Maggiore della Carità”, Ematologia, Novara, Italy,

Università degli Studi

di Modena e Reggio Emilia, Centro Oncologico Modenese, Modena, Italy,

Hospital Clínic Universitari, Department of Hematology, Barcelona,

Spain,

Northwestern Medicine, Hematology and Medical Oncology,

Chicago, Illinois, USA,

Foundation for the Institute of Oncology Research

(IOR), International Extranodal Lymphoma Study Group, Oncology Insti-

tute of Southern Switzerland, Medical Oncology Clinic, Bellinzona,

Switzerland

130

SUPPLEMENT ABSTRACTS

Characteristics at diagnosis and clinical course of primary extra-

nodal follicular lymphoma (EFL) was never extensively described.

The International Extranodal Lymphoma Study Group (IELSG) co-

ordinated an international multicenter retrospective survey aimed

to describe the clinical features at diagnosis and outcome of a

population of EFL. A dataset, including 608 pathologically reviewed

cases from 19 different countries was analyzed, their outcome was

compared to the outcome of a population of nodal follicular lym-

phomas. Skin (n =334), gastrointestinal tract (n =72), 22 of whom

with a primary duodenal localization, were the two most frequent

presentation sites. These subsets displayed peculiar features at

diagnosis and signiﬁcantly different pattern of survival. After me-

dian follow‐up of 5.‐years, a superior outcome was observed for

primary cutaneous lymphomas [10‐yr OS:89% (95%CI, 83‐93%)]

and intermediate outcome for primary gastrointestinal lymphomas

[10‐yr OS:79% [95%CI, 59‐90%)] among whom primary duodenal

lymphomas displayed a trend toward the best outcome [10‐yr

OS:95% (95%CI, 72‐99%)]. All the other primary extranodal sites

presented an inferior outcome [10‐yr OS: 59% (95%CI, 48‐68%)]

analogous to the outcome of primary nodal lymphomas [10‐yr

OS:57% (95%CI: 49‐64%)]. These ﬁndings support the hypothesis

that some primary lymphoma localizations may represent speciﬁc

entities.

Keywords: Extranodal non‐Hodgkin lymphoma

Conﬂicts of interests pertinent to the abstract

A. Janikova

Consultant or advisory role: Novartis, Roche, Gilead

Honoraria: Gilead, Roche

079 |PHASE II TRIAL OF RITUXIMAB PLUS CHLORAMBUCIL

FOLLOWED BY A 2‐YEAR SUBCUTANEOUS RITUXIMAB

MAINTENANCE IN MALT LYMPHOMA PATIENTS (IELSG38)

M. C. Pirosa

, L. Orsucci

, P. Feugier

, M. Tani

, Hervé Ghesquieres

G. Musuraca

, L. Baldini

, F. Merli

, B. De Renzis

, E. Gyan

G. Gini

, D. Marino

, R. Gressin

, F. Morschhauser

, F. Palombi

F. Cavallo

, A. Conconi

, S. Le Gouill

, Hervé Tilly

, M. Zanni

M. G. Cabras

, E. Capochiani

, C. Califano

, A. L. Molinari

A. Pulsoni

, F. Angrilli

, G. Cartron

, O. Casasnovas

, L. Devizzi

C. Haioun

, R. Houot

, A. M. Liberati

, U. Occhini

, M. Merli

G. Pietrantuono

, F. Re

, M. Spina

, F. Esposito

, F. Bertoni

D. Rossi

, N. Ielmini

, S. Luminari

, F. Cavalli

, E. Zucca

A. Stathis

, C. Thieblemont

Oncology Institute of Southern Switzerland, Hematology, Bellinzona,

Switzerland,

A.O.U. Città della Salute e della Scienza di Torino,

Dipartimento di Oncologia ed Ematologia, Torino, Italy,

CHU Nancy‐

Brabois, Hématologie, Nancy, France,

Ospedale Santa Maria delle

Croci, Dipartimento di Oncologia ed Ematologia, Ravenna, Italy,

Centre Hospitalier Universitaire de Lyon, Hôpital Lyon Sud ‐Héma-

tologie, Pierre‐Bénite, France,

IRCCS Istituto Romagnolo per lo Studio

dei Tumori "Dino Amadori" IRST S.r.l., Ematologia, Meldola, Italy,

Fondazione IRCCS Cà Granda, Ospedale Maggiore Policlinico ‐Ema-

tologia, Milano, Italy,

Arcispedale Santa Maria Nuova, Servizio di

Ematologia, Reggio Emilia, Italy,

CHU Estaing, Service d’Hématologie

Clinique, Clermont‐Ferrant, France,

CHU de Tours, Service d’héma-

tologie, Tours, France,

AU Ospedali Riuniti Ancona, Clinica di Ema-

tologia, Ancona, Italy,

Istituto Oncologico Veneto ‐IRCCS, UOC

Oncologia 1, Padova, Italy,

CHU Crenoble Alpes, Service Hématologie,

Grenoble, France,

CHU de Lille ‐Hôpital Claude Huriez, Service des

SUPPLEMENT ABSTRACTS

131